Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sequence and Structure Analysis
2.2. Genomic Variant Analysis
2.3. SOX18 Culture Experiments
3. Results
3.1. Sequence Evolution of SOX Genes/Proteins
Gene | Group | Ensembl | NCBI | Missense Constraint | OMIM/ClinVar | Inheritance | AA | Species NA | Species AA | gnomAD | ClinVar | Geno2MP | COSMIC |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SOX1 | B | ENST00000330949 | NP 005977 | 0.58 | - | - | 391 | 73 | 348 | 120 | 0 | 115 | 134 |
SOX2 | B | ENST00000325404 | NP 003097 | 2.12 | Microphthalmia | AD | 317 | 88 | 452 | 119 | 70 | 66 | 203 |
SOX3 | B | ENST00000370536 | NP 005625 | 2.21 | Panhypopituitarism | XL | 446 | 74 | 194 | 104 | 18 | 39 | 226 |
SRY | A | ENST00000383070 | NP 003131 | −0.14 | sex reversal | XLD | 204 | 30 | 57 | 25 | 26 | 5 | 25 |
SOX14 | B | ENST00000306087 | NP 004180 | 1.14 | - | - | 240 | 100 | 465 | 118 | 0 | 20 | 112 |
SOX21 | B | ENST00000376945 | NP 009015 | 1.74 | - | - | 276 | 104 | 388 | 81 | 0 | 60 | 79 |
SOX4 | C | ENST00000244745 | NP 003098 | 1.17 | Coffin-Siris syndrome | AD | 474 | 103 | 281 | 210 | 27 | 64 | 125 |
SOX11 | C | ENST00000322002 | NP 003099 | 2.26 | Coffin-Siris syndrome | AD | 441 | 122 | 420 | 166 | 47 | 38 | 282 |
SOX12 | C | ENST00000342665 | NP 008874 | 1.79 | - | - | 315 | 71 | 261 | 106 | 1 | 27 | 63 |
SOX5 | D | ENST00000451604 | NP 008871 | 3.15 | Lamb-Shaffer syndrome | AD | 763 | 89 | 445 | 264 | 46 | 51 | 480 |
SOX6 | D | ENST00000528429 | NP 001354802 | 1.94 | Tolchin-Le Caignec syndrome | AD | 828 | 101 | 438 | 365 | 17 | 86 | 380 |
SOX13 | D | ENST00000367204 | NP 005677 | 1.74 | - | - | 622 | 94 | 321 | 296 | 0 | 91 | 199 |
SOX8 | E | ENST00000293894 | NP 055402 | 0.89 | - | - | 446 | 143 | 301 | 254 | 3 | 98 | 183 |
SOX9 | E | ENST00000245479 | NP 000337 | 1.63 | Campomelic dysplasia | AD | 509 | 112 | 375 | 259 | 97 | 55 | 524 |
SOX10 | E | ENST00000396884 | NP 008872 | 2.77 | PCWH syndrome | AD | 466 | 100 | 434 | 176 | 100 | 44 | 198 |
SOX7 | F | ENST0000030450 | NP 113627 | −0.74 | - | - | 388 | 149 | 444 | 420 | 2 | 81 | 204 |
SOX17 | F | ENST00000297316 | NP 071899 | 0.77 | Vesicoureteral reflux | AD | 414 | 100 | 227 | 225 | 18 | 63 | 424 |
SOX18 | F | ENST00000340356 | NP 060889 | 0.86 | HLTS | AD/AR | 384 | 102 | 287 | 151 | 9 | 75 | 93 |
SOX15 | G | ENST00000250055 | NP 008873 | 0.62 | - | - | 233 | 97 | 210 | 118 | 0 | 29 | 83 |
SOX30 | H | ENST00000265007 | NP 848511 | 0.78 | Male infertility | AD | 753 | 111 | 319 | 422 | 4 | 67 | 296 |
Average | 1 | Total | 8910 | 1963 | 6667 | 3999 | 485 | 1174 | 4313 |
3.2. Mapping SOX Variants
3.3. Interpreting HMG Box Variants
3.4. HMG Box Variant SOX18 E137K
3.5. Functional SOX Variants Outside the HMG Box
3.6. Somatic SOX Variants in Cancer
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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UniProt | Bowles/Koopman | AA Used | AA Used | AA Conservation | Publications | Unique ClinVar | gnomAD Count | HPO Profiles | Variant | Syn (s) | Nonsyn (n) | Conservation Score |
---|---|---|---|---|---|---|---|---|---|---|---|---|
−1 | 2 | 3 | RHK | 0.93 ± 0.08 | 2 | 6 | 1 | SOX4 H58P | 4 | 0 | 1 | |
1 | 3 | 2 | VI | 0.92 ± 0.09 | 3 | 3 | 6 | 3 | SOX4 I59S | 7 | 0 | 1.25 |
SOX9 V105F | 11 | 0 | 1 | |||||||||
2 | 4 | 2 | KR | 0.94 ± 0.07 | 3 | 3 | 1 | SOX3 K140R | 10 | 0 | 2 | |
SOX9 K106E | 9 | 0 | 1.25 | |||||||||
SOX10 K105Q | 4 | 0 | 1 | |||||||||
3 | 5 | 1 | R | 0.94 ± 0.07 | 2 | 10 | 2 | 0 | SOX4 R61Q | 22 | 0 | 1.5 |
SOX5 R558H | 10 | 0 | 1.25 | |||||||||
SOX6 R623Q | 9 | 0 | 1.25 | |||||||||
SOX10 R106G | 15 | 0 | 1.25 | |||||||||
5 | 7 | 1 | M | 0.95 ± 0.05 | 2 | 4 | 21 | 2 | SOX6 M625T | 0 | 0 | 1 |
SOX10 M108T | 0 | 0 | 1 | |||||||||
6 | 8 | 1 | N | 0.95 ± 0.05 | 3 | 1152 | 1 | SOX5 N561H | 10 | 0 | 1.5 | |
SOX10 N109S | 16 | 0 | 2 | |||||||||
7 | 9 | 1 | A | 0.95 ± 0.05 | 4 | 2 | 0 | SRY A66P | 6 | 0 | 1.5 | |
SOX4 A65T | 17 | 0 | 1.25 | |||||||||
SOX9 A111T | 13 | 0 | 1 | |||||||||
SOX10 A110V | 2 | 0 | 1 | |||||||||
9 | 11 | 2 | MI | 0.95 ± 0.04 | 4 | 9 | 4 | 0 | SOX9 M113V/I | 0 | 0 | 1 |
SOX10 M112V/R/T/I | 0 | 0 | 1 | |||||||||
10 | 12 | 1 | V | 0.95 ± 0.04 | 1 | 5 | 0 | SOX9 V114L | 12 | 0 | 1 | |
11 | 13 | 1 | W | 0.95 ± 0.06 | 1 | 4 | 1 | 0 | SOX11 W59R | 0 | 0 | 1 |
SOX9 W115R | 0 | 0 | 1 | |||||||||
SOX6 W631C | 0 | 0 | 1 | |||||||||
12 | 14 | 2 | SA | 0.96 ± 0.03 | 5 | 2 | 0 | SOX11 S60P | 20 | 0 | 1.5 | |
SOX9 A116V | 23 | 0 | 1.5 | |||||||||
15 | 17 | 4 | QEAH | 0.95 ± 0.04 | 1 | 1 | 29 | 2 | SOX9 A119E | 15 | 0 | 1.25 |
16 | 18 | 1 | R | 0.95 ± 0.04 | 10 | 4 | 0 | SOX2 R56G/W | 13 | 0 | 1.25 | |
SOX9 R120G/L | 20 | 0 | 1.25 | |||||||||
SOX11 R64C/G/H | 16 | 0 | 1.25 | |||||||||
SOX10 R119L | 8 | 0 | 1 | |||||||||
SOX5 R571L/W | 16 | 0 | 1.25 | |||||||||
19 | 21 | 3 | MIL | 0.93 ± 0.08 | 1 | 2 | 6 | 0 | SOX4 I77V | 12 | 0 | 1.5 |
SOX10 L122V | 20 | 0 | 1.25 | |||||||||
20 | 22 | 3 | AML | 0.94 ± 0.09 | 1 | 4 | 9 | 0 | SOX9 A124P | 35 | 1 | 1 |
SOX10 A123P | 15 | 0 | 1.25 | |||||||||
24 | 26 | 1 | P | 0.94 ± 0.10 | 1 | 14 | 6 | SRY P83H | 2 | 0 | 1.25 | |
26 | 28 | 3 | MLA | 0.94 ± 0.09 | 3 | 10 | 2 | SOX10 L129P | 11 | 0 | 1 | |
28 | 30 | 1 | N | 0.94 ± 0.09 | 2 | 3 | 16 | 0 | SOX11 N76D | 4 | 0 | 1 |
SOX5 N583S | 9 | 0 | 1.25 | |||||||||
SOX17 N95S | 9 | 0 | 1.5 | |||||||||
29 | 31 | 2 | SA | 0.94 ± 0.08 | 2 | 3 | 0 | SOX10 A132G/V | 19 | 0 | 1.5 | |
31 | 33 | 2 | IL | 0.94 ± 0.10 | 3 | 3 | 4 | 2 | SOX11 I79L | 12 | 0 | 1.5 |
SOX10 L134P | 4 | 0 | 1 | |||||||||
32 | 34 | 1 | S | 0.94 ± 0.11 | 1 | 7 | 3 | 0 | SOX11 S80F/C | 2 | 0 | 1 |
SOX5 S587C | 1 | 0 | 1 | |||||||||
SOX10 S135R/G/T | 5 | 0 | 1 | |||||||||
33 | 35 | 2 | KV | 0.93 ± 0.10 | 1 | 1 | 0 | 0 | SOX5 K588N | 5 | 0 | 1 |
34 | 36 | 5 | RQITM | 0.95 ± 0.06 | 2 | 21 | 9 | SOX2 R74P | 16 | 0 | 1.5 | |
SOX9 T138K | 27 | 0 | 1.5 | |||||||||
35 | 37 | 1 | L | 0.95 ± 0.07 | 1 | 1 | 1 | 1 | SOX4 L93Q | 11 | 0 | 1 |
36 | 38 | 1 | G | 0.95 ± 0.07 | 2 | 6 | 3 | 2 | SOX2 G76D | 8 | 0 | 1.25 |
SRY G95R/E | 2 | 0 | 1.25 | |||||||||
SOX9 G140D | 14 | 0 | 1 | |||||||||
SOX10 G139C/D | 10 | 0 | 1 | |||||||||
38 | 40 | 7 | EDQRLSA | 0.93 ± 0.10 | 2 | 23 | 3 | SOX10 L141P | 11 | 0 | 1 | |
39 | 41 | 1 | W | 0.96 ± 0.06 | 1 | 7 | 1 | 0 | SOX4 W97G | 0 | 0 | 1 |
SOX6 W659R | 0 | 0 | 1 | |||||||||
SOX10 W142R/S/C | 0 | 0 | 1 | |||||||||
47 | 49 | 1 | K | 0.96 ± 0.06 | 2 | 3 | 24 | 0 | SRY K106I | 1 | 0 | 1.25 |
SOX10 K150E | 5 | 0 | 1 | |||||||||
SOX4 K105N | 1 | 0 | 1 | |||||||||
48 | 50 | 5 | RWIQK | 0.96 ± 0.05 | 1 | 2 | 12 | 0 | SOX10 R151P | 15 | 0 | 1.25 |
50 | 52 | 2 | FY | 0.96 ± 0.02 | 2 | 5 | 11 | 0 | SRY F109S | 2 | 0 | 1.25 |
SOX9 F154L | 14 | 0 | 1.5 | |||||||||
SOX10 F153I | 13 | 0 | 1.5 | |||||||||
52 | 54 | 4 | DQRE | 0.92 ± 0.13 | 2 | 11 | 1 | SOX10 E155K | 6 | 0 | 1 | |
53 | 55 | 1 | E | 0.97 ± 0.02 | 1 | 285 | 16 | SOX18 E137K | 10 | 0 | 2 | |
54 | 56 | 2 | AQ | 0.97 ± 0.03 | 3 | 6 | 9 | 1 | SRY A113T | 5 | 0 | 1.5 |
SOX11 A102V | 16 | 0 | 1.25 | |||||||||
SOX10 A157V | 28 | 0 | 2 | |||||||||
SOX4 A112P | 11 | 0 | 1.25 | |||||||||
55 | 57 | 4 | KQEA | 0.96 ± 0.04 | 2 | 9 | 1 | SOX17 E122D | 3 | 0 | 1 | |
56 | 58 | 2 | RK | 0.96 ± 0.07 | 4 | 14 | 4 | SOX2 R96P | 6 | 0 | 1 | |
SOX9 R160P | 19 | 0 | 1.25 | |||||||||
SOX5 R611G | 22 | 0 | 1.5 | |||||||||
SOX6 R676Q | 13 | 0 | 1.25 | |||||||||
57 | 59 | 2 | LI | 0.97 ± 0.01 | 2 | 0 | 0 | SOX2 L97P | 5 | 0 | 1 | |
SOX10 L160P | 12 | 0 | 1 | |||||||||
58 | 60 | 4 | RQSK | 0.97 ± 0.02 | 1 | 3 | 76 | 2 | SOX10 R161C/H | 15 | 0 | 1.25 |
SOX17 R125S | 18 | 0 | 1.25 | |||||||||
61 | 63 | 1 | H | 0.95 ± 0.10 | 2 | 4 | 3 | 0 | SOX2 H101R | 1 | 0 | 1 |
SOX9 H165Y/R | 7 | 0 | 1.25 | |||||||||
SOX10 H164P | 5 | 0 | 1 | |||||||||
63 | 65 | 5 | KEAQR | 0.94 ± 0.10 | 1 | 26 | 2 | SOX10 K166E | 11 | 0 | 1.25 | |
65 | 67 | 3 | HYF | 0.95 ± 0.06 | 2 | 4 | 3 | SOX11 Y113C | 16 | 1 | 1 | |
68 | 70 | 2 | YW | 0.95 ± 0.08 | 3 | 6 | 4 | 0 | SOX11 Y116C | 3 | 0 | 1 |
SOX17 Y135C | 3 | 0 | 1 | |||||||||
70 | 72 | 1 | Y | 0.95 ± 0.11 | 4 | 0 | 0 | SOX4 Y128H | 2 | 0 | 1 | |
71 | 73 | 3 | RKQ | 0.95 ± 0.08 | 1 | 3 | 11 | 4 | SOX10 Q174P | 8 | 0 | 1.25 |
72 | 74 | 1 | P | 0.93 ± 0.13 | 4 | 9 | 4 | 0 | SOX2 P112T/A | 11 | 0 | 1.25 |
SOX11 P120L | 13 | 0 | 1.25 | |||||||||
SOX9 P176T/S/L/R | 35 | 1 | 1 | |||||||||
SOX6 P692S | 11 | 0 | 1.25 | |||||||||
SOX10 P175S | 17 | 0 | 1.25 | |||||||||
73 | 75 | 1 | R | 0.91 ± 0.14 | 3 | 25 | 4 | SOX2 R113W | 4 | 0 | 1 | |
74 | 76 | 3 | RKP | 0.92 ± 0.13 | 1 | 3 | 6 | 0 | SOX10 R177Q | 25 | 0 | 1.5 |
Gene | Geno2MP Var | HMG Box # | AA Used in Human | AA Conservation | Genes with ClinVar | Phenotype | Geno2MP HPO | Geno2MP CADD | gnomAD Count | Syn (s) | Nonsyn (n) | Conservation Score |
---|---|---|---|---|---|---|---|---|---|---|---|---|
SOX1 | E88A | 38 | 7 | 0.93 ± 0.10 | 2 | Microcephaly | 1 | 21.6 | 4 | 5 | 0 | 1.5 |
SOX10 | H128Q | 25 | 5 | 0.93 ± 0.10 | 1 | Abnormality of the ear | 1 | 23.8 | 0 | 4 | 0 | 1 |
SOX10 | L138P | 35 | 1 | 0.95 ± 0.07 | 1 | Nephrotic syndrome | 1 | 21.2 | 0 | 11 | 0 | 1 |
SOX11 | G84S | 36 | 1 | 0.95 ± 0.07 | 4 | Abnormality of the globe | 1 | 28.5 | 0 | 13 | 0 | 1.25 |
SOX13 | Q444E | 21 | 6 | 0.92 ± 0.09 | 0 | Abnormality of the limb | 2 | 28.6 | 1 | 16.5 | 2.5 | 1 |
SOX13 | R461H | 38 | 7 | 0.93 ± 0.10 | 2 | Hypoplastic left-heart | 2 | 34 | 8 | 17 | 0 | 1.25 |
SOX13 | A478E | 55 | 4 | 0.96 ± 0.04 | 2 | Retinitis pigmentosa | 1 | 28.5 | 2 | 24 | 0 | 1.5 |
SOX14 | R63Q | 56 | 2 | 0.96 ± 0.07 | 4 | Congenital diaphragmatic hernia | 2 | 29.2 | 1 | 19 | 1 | 1 |
SOX14 | R80Q | 73 | 1 | 0.91 ± 0.14 | 2 | Abnormal muscle physiology (×2) | 3 | 26 | 0 | 11 | 0 | 1.25 |
SOX15 | R82L | 34 | 5 | 0.95 ± 0.06 | 2 | Retinitis pigmentosa | 2 | 36 | 9 | 7 | 0 | 1.25 |
SOX15 | G84D | 36 | 1 | 0.95 ± 0.07 | 4 | Tricuspid atresia | 1 | 33 | 2 | 11 | 0 | 1.25 |
SOX15 | R104G | 56 | 2 | 0.96 ± 0.07 | 4 | Progressive muscle weakness | 2 | 27.2 | 0 | 14 | 0 | 1.25 |
SOX17 | M101V | 34 | 5 | 0.95 ± 0.06 | 2 | Distal arthrogryposis | 1 | 23.2 | 0 | 0 | 0 | 1 |
SOX17 | R125S | 58 | 4 | 0.97 ± 0.02 | 2 | Neural Atrophy/Degeneration | 1 | 33 | 4 | 18 | 0 | 1.25 |
SOX18 | E137K | 53 | 1 | 0.97 ± 0.02 | 1 | Seizures (×2), DD/ID, ASD, brain morphology, heart | 16 | 28.6 | 278 | 10 | 0 | 2 |
SOX18 | N151S | 67 | 3 | 0.95 ± 0.05 | 0 | abdominal organs | 1 | 24 | 1 | 3 | 0 | 1 |
SOX18 | R155Q | 71 | 3 | 0.95 ± 0.08 | 2 | Malformation of the heart (×2) | 3 | 26.6 | 1 | 15 | 0 | 1.25 |
SOX30 | I367V | 31 | 2 | 0.94 ± 0.10 | 3 | ASD, Cerebellar hypoplasia (×2) | 2 | 22.5 | 0 | 3 | 0 | 1 |
SOX30 | E399A | 63 | 5 | 0.94 ± 0.10 | 1 | cardiovascular system | 1 | 24.5 | 3 | 7 | 0 | 1.5 |
SOX6 | D607E | 14 | 5 | 0.91 ± 0.13 | 0 | Abnormality of the cerebral cortex | 1 | 25.1 | 0 | 16 | 0 | 2 |
SOX6 | M619T | 26 | 3 | 0.94 ± 0.09 | 3 | Thoracic aortic aneurysm | 1 | 21.5 | 0 | 0 | 0 | 1 |
SOX7 | K81R | 37 | 6 | 0.92 ± 0.12 | 0 | Spontaneous abortion | 2 | 22.2 | 1 | 12 | 0 | 1.25 |
SOX7 | A98G | 54 | 2 | 0.97 ± 0.03 | 5 | Abnormality of hindbrain morphology | 1 | 27.8 | 1 | 33 | 0 | 1.5 |
SOX7 | D108N | 64 | 3 | 0.95 ± 0.11 | 2 | central nervous system | 2 | 35 | 3 | 17 | 0 | 1.5 |
SOX8 | R159G | 58 | 4 | 0.97 ± 0.02 | 2 | Intellectual disability, microcephaly (×2) | 1 | 20.8 | 1 | 40 | 0 | 1.5 |
SOX8 | K163R | 62 | 4 | 0.96 ± 0.02 | 0 | Nephrotic syndrome | 1 | 35 | 5 | 10 | 0 | 1.25 |
Gene | Codon # | AA | Var | Phenotype | Syn (s) | Nonsyn (n) | Selection Score | 21 Codon Window | AA Conservation | gnomAD Count | Geno2MP | HPO Profiles | CADD |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SOX1 | 126 | T | T126I | Abnormality of hindbrain morphology | 1 | 0 | 1 | 25.25 | 0.97 | 1 | T126I | 1 | 21.7 |
SOX2 | 123 | D | D123G | Developmental disorder | 4 | 0 | 1.25 | 17.5 | 1.00 | 1 | |||
SOX2 | 130 | G | G130A | abnormalities of the central nervous system | 8 | 0 | 1.25 | 15.25 | 0.99 | 17 | G130A | 1 | 23.3 |
SOX2 | 133 | A | A133T | Anophthalmia/microphthalmia-esophageal atresia syndrome | 22 | 0 | 2 | 11.25 | 0.96 | 8 | A133T | 3 | 23.3 |
SOX2 | 272 | D | D272N | not provided | 1 | 0 | 1 | 13.75 | 0.97 | ||||
SOX5 | 135 | R | R122H | Intellectual disability | 10 | 0 | 1.25 | 23.75 | 0.94 | 1 | R122H | 1 | 35 |
SOX5 | 159 | P | P146L | Thoracic aortic aneurysm | 10 | 0 | 1.25 | 14.75 | 0.94 | 1 | P146L | 1 | 25.1 |
SOX5 | 206 | I | I206V | Lamb-Shaffer syndrome | 4 | 0 | 1 | 19.75 | 0.95 | ||||
SOX5 | 228 | A | A215V | Coarctation of aorta | 22 | 0 | 1.5 | 20.5 | 0.95 | 10 | A215V | 1 | 33 |
SOX5 | 261 | K | K261N | not provided | 4 | 0 | 1 | 22.5 | 0.96 | ||||
SOX5 | 266 | Q | Q266H | Lamb-Shaffer syndrome | 7 | 0 | 1.25 | 16.25 | 0.96 | ||||
SOX5 | 268 | Q | Q268H | Lamb-Shaffer syndrome | 5 | 0 | 1 | 14.5 | 0.96 | ||||
SOX6 | 146 | E | E146K | not provided | 10 | 0 | 1.5 | 13 | 0.95 | 2 | E146D | 2 | 20.4 |
SOX6 | 209 | H | H209K | Multiple neurological | 16 | 0 | 2 | 22.25 | 0.97 | ||||
SOX6 | 214 | K | K214Q | Hypoplastic left-heart syndrome | 8 | 0 | 1.25 | 23.5 | 0.97 | 4 | K214Q | 2 | 22 |
SOX6 | 252 | N | N252K | not provided | 3 | 0 | 1 | 18.25 | 0.97 | ||||
SOX6 | 264 | M | M264I | myopathy | 0 | 0 | 1 | 17.25 | 0.96 | 5 | M264I | 1 | 22.1 |
SOX6 | 277 | R | R277W | not provided | 7 | 0 | 1 | 19.75 | 0.97 | 14 | |||
SOX6 | 280 | A | A280E | Aplasia/Hypoplasia affecting the eye | 4 | 0 | 1 | 18.75 | 0.97 | 1 | A280E | 2 | 23.1 |
SOX6 | 281 | A | A281T | not provided | 8 | 0 | 1.25 | 19 | 0.97 | 1 | |||
SOX6 | 291 | F | F291L | cardiovascular system | 7 | 0 | 1.25 | 17 | 0.97 | 5 | F291L | 1 | 22.4 |
SOX6 | 310 | S | S310T | Microcephaly | 5 | 0 | 1 | 13.25 | 0.97 | 56 | S310T | 2 | 21.6 |
SOX6 | 312 | M | M312V | not provided | 0 | 0 | 1 | 13.75 | 0.95 | ||||
SOX6 | 371 | A | A330P | Aplasia/Hypoplasia affecting the eye | 10 | 0 | 1.25 | 14 | 0.99 | 1 | A330P | 1 | 23.9 |
SOX6 | 512 | R | R485Q | Abnormality of nervous system | 12 | 0 | 1.25 | 17 | 0.99 | 2 | R485Q | 1 | 28.5 |
SOX6 | 572 | R | R545Q | Intellectual disability | 9 | 0 | 1.25 | 15 | 0.99 | 6 | R545Q | 1 | 32 |
SOX6 | 618 | E | E591K | Intellectual disability | 10 | 0 | 1.5 | 20.25 | 0.98 | 1 | E591K | 1 | 35 |
SOX7 | 128 | R | R128C | abnormality of the central nervous system | 30 | 0 | 1.5 | 12 | 0.99 | 4 | R128C | 1 | 21.8 |
SOX7 | 329 | R | R329H | Nephrotic syndrome | 19 | 0 | 1.25 | 15.25 | 1.00 | 3 | R329H | 1 | 25.3 |
SOX7 | 379 | A | A379V | Abnormality of the eye (×4) | 25 | 0 | 1.25 | 21 | 0.99 | 195 | A379V | 9 | 29 |
SOX8 | 263 | N | N263I | Abnormality of the nervous system (×2) | 17 | 0 | 1.25 | 13.25 | 0.99 | 45 | N263I | 6 | 24.1 |
SOX9 | 73 | I | I73T | Campomelic dysplasia | 2 | 0 | 1 | 14.25 | 0.97 | ||||
SOX9 | 76 | A | A76E | Inborn genetic diseases | 32 | 0 | 2 | 17 | 0.97 | ||||
SOX9 | 81 | L | L81V | Campomelic dysplasia | 20 | 0 | 1.25 | 18.25 | 0.97 | 1 | |||
SOX9 | 83 | G | G83R | Inborn genetic diseases | 10 | 0 | 1 | 20.25 | 0.97 | ||||
SOX10 | 68 | F | F68L | PCWH syndrome | 4 | 0 | 1 | 12.5 | 0.96 | 1 | |||
SOX10 | 75 | A | A75V | Malformation of the heart and great vessels (×2) | 20 | 0 | 1.5 | 17.25 | 0.96 | A75V | 2 | 34 | |
SOX10 | 92 | V | V92M/L | PCWH syndrome | 7 | 0 | 1 | 17.5 | 0.97 | 46 | V92L | 4 | 24.1 |
SOX10 | 179 | K | K179N | not provided | 3 | 0 | 1 | 19.25 | 1.00 | ||||
SOX10 | 181 | G | G181R | not provided | 9 | 0 | 1 | 17.5 | 0.98 | 1 | |||
SOX10 | 216 | H | H216Q | not provided | 4 | 0 | 1 | 13 | 0.74 | ||||
SOX10 | 240 | T | T240P | Waardenburg syndrome type 4C | 12 | 0 | 1.25 | 16.25 | 1.00 | ||||
SOX10 | 278 | I | I278V | Aganglionic megacolon | 15 | 0 | 1.5 | 12.75 | 1.00 | 25 | |||
SOX10 | 428 | M | M428I | Abnormality of limb bone | 0 | 0 | 1 | 15.75 | 0.99 | 14 | M428I | 2 | 22.7 |
SOX10 | 433 | R | R433Q | not provided | 6 | 0 | 1 | 19.5 | 0.99 | 2 | |||
SOX11 | 417 | C | C417W | not provided | 4 | 0 | 1 | 17.25 | 0.95 | ||||
SOX13 | 171 | S | S171L | Abnormality of the ear | 36 | 2 | 1 | 13 | 0.99 | 2 | S171L | 1 | 26.3 |
SOX13 | 192 | R | R192Q | Multiple | 15 | 0 | 1.25 | 22.25 | 0.99 | 4 | R192Q | 5 | 34 |
SOX13 | 210 | H | H210R | Neural Atrophy/Degeneration | 13 | 0 | 1.5 | 21.25 | 0.98 | 4 | H210R | 4 | 26.7 |
SOX13 | 507 | R | R507Q | Muscular dystrophy | 16 | 0 | 1.25 | 19.5 | 0.96 | 3 | R507Q | 2 | 34 |
SOX14 | 88 | K | K88R | Abnormality of the cardiovascular system (×9) | 4 | 0 | 1 | 23 | 0.95 | 52 | K88R | 8 | 25.8 |
SOX14 | 187 | T | T187K | Hypoplastic left-heart syndrome | 5 | 0 | 1 | 21 | 1.00 | 1 | T187K | 2 | 25.4 |
SOX18 | 326 | E | E326V | Skeletal muscle atrophy | 1 | 0 | 1 | 10.25 | 1.00 | E326V | 1 | 21.4 | |
SOX18 | 331 | L | L331F | HLTS | 9 | 0 | 1 | 11 | 1.00 | ||||
SOX18 | 369 | L | L369V | not provided | 19 | 0 | 1.25 | 16 | 1.00 | 1 | |||
SOX18 | 375 | A | A375T | Nephrotic syndrome | 35 | 0 | 2 | 13.25 | 0.99 | A375T | 1 | 20.4 |
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Underwood, A.; Rasicci, D.T.; Hinds, D.; Mitchell, J.T.; Zieba, J.K.; Mills, J.; Arnold, N.E.; Cook, T.W.; Moustaqil, M.; Gambin, Y.; et al. Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships. Genes 2023, 14, 222. https://doi.org/10.3390/genes14010222
Underwood A, Rasicci DT, Hinds D, Mitchell JT, Zieba JK, Mills J, Arnold NE, Cook TW, Moustaqil M, Gambin Y, et al. Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships. Genes. 2023; 14(1):222. https://doi.org/10.3390/genes14010222
Chicago/Turabian StyleUnderwood, Adam, Daniel T Rasicci, David Hinds, Jackson T Mitchell, Jacob K Zieba, Joshua Mills, Nicholas E Arnold, Taylor W Cook, Mehdi Moustaqil, Yann Gambin, and et al. 2023. "Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships" Genes 14, no. 1: 222. https://doi.org/10.3390/genes14010222
APA StyleUnderwood, A., Rasicci, D. T., Hinds, D., Mitchell, J. T., Zieba, J. K., Mills, J., Arnold, N. E., Cook, T. W., Moustaqil, M., Gambin, Y., Sierecki, E., Fontaine, F., Vanderweele, S., Das, A. S., Cvammen, W., Sirpilla, O., Soehnlen, X., Bricker, K., Alokaili, M., ... Prokop, J. W. (2023). Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships. Genes, 14(1), 222. https://doi.org/10.3390/genes14010222