SOX21

Chr 13

SRY-box transcription factor 21

Also known as: SOX-A, SOX25

NCBI Gene: 11166 ENSG00000125285 UniProt: Q9Y651

SOX21 encodes a transcription factor that contains an HMG DNA-binding domain and can activate transcription of the opioid receptor OPRM1, with additional roles in ameloblast differentiation for tooth development. The gene shows moderate constraint against loss-of-function variants (pLI = 0.71, LOEUF = 0.73), but associated human diseases have not yet been definitively established in the medical literature.

ResearchSummary from RefSeq, UniProt

SRY-related HMG-box (SOX) genes encode a family of DNA-binding proteins containing a 79-amino acid HMG (high mobility group) domain that shares at least 50% sequence identity with the DNA-binding HMG box of the SRY protein (MIM 480000). SOX proteins are divided into 6 subgroups based on sequence similarity within and outside of the HMG domain. For additional background information on SOX genes, see SOX1 (MIM 602148).[supplied by OMIM, Apr 2004]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.73

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.73LOEUF

pLI 0.713

Z-score 1.88

OE 0.00 (0.00–0.73)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

1.74Z-score

OE missense 0.52 (0.42–0.65)

55 obs / 105.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.73)

0≤0.351.4

Missense OE?0.52 (0.42–0.65)

0≤0.61.4

Synonymous OE?0.66

0≤1.21.6

LoF obs/exp: 0 / 4.1Missense obs/exp: 55 / 105.3Syn Z: 1.89

Background carrier burden — how many people carry a rare variant somewhere in SOX21?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

402 rare PASS variants

Rare truncating (LoF)

1 in 230

60 rare PASS variants

Rare synonymous (reference)

1 in 120

258 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SOX21; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 320
South Asian	~43k	1 in 140	1 in 340
Remaining (unassigned)	~30k	1 in 240	1 in 130
European (Finnish)	~27k	1 in 320	1 in 150
Admixed American	~22k	1 in 120	1 in 550
African / African American	~21k	1 in 290	1 in 290
East Asian	~20k	1 in 120	1 in 120
Ashkenazi Jewish	~13k	1 in 570	1 in 170
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 0 of 1 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 1.? see exons ↓