SOX14

Chr 3

SRY-box transcription factor 14

Also known as: SOX28

NCBI Gene: 8403 ENSG00000168875 UniProt: O95416 OMIM: 604747

This intronless gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. Mutations in this gene are suggested to be responsible for the limb defects associated with blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) and Mobius syndrome. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM 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

0.47

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.856

Z-score 2.33

OE 0.00 (0.00–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.14Z-score

OE missense 0.73 (0.63–0.86)

107 obs / 145.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.47)

0≤0.351.4

Missense OE?0.73 (0.63–0.86)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 0 / 6.3Missense obs/exp: 107 / 145.8Syn Z: 0.10

Background carrier burden — how many people carry a rare variant somewhere in SOX14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 360

288 rare PASS variants

Rare truncating (LoF)

1 in 17,000

14 rare PASS variants

Rare synonymous (reference)

1 in 300

172 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SOX14. 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 380	1 in 20,000
South Asian	~43k	1 in 430	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 460	none seen
European (Finnish)	~27k	1 in 1,300	none seen
Admixed American	~22k	1 in 280	≈ 1 in 7,600
African / African American	~21k	1 in 440	≈ 1 in 6,000
East Asian	~20k	1 in 260	none seen
Ashkenazi Jewish	~13k	1 in 380	none seen
Middle Eastern	~2,884	1 in 580	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): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓