SOX11

Chr 2AD

SRY-box transcription factor 11

Also known as: CSS9, IDDMOH, MRD27

NCBI Gene: 6664 ENSG00000176887 UniProt: P35716 OMIM: 600898

SOX11 encodes a transcription factor that binds to gene promoters to activate transcription and plays a critical role in cell survival during development of the neural tube, branchial arches, and somites. Mutations cause autosomal dominant intellectual developmental disorder with microcephaly and variable features including ocular malformations or hypogonadotropic hypogonadism. The gene is highly constrained against loss-of-function variants, reflecting its essential role in neurodevelopment.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. The protein may function in the developing nervous system and play a role in tumorigenesis. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.441 OMIM phenotype

Clinical Summary— SOX11

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Gene-Disease Validity (ClinGen)

SOX11-related complex neurodevelopmental disorder with or without congenital anomalies · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.

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ClinVar Variants

86 unique Pathogenic / Likely Pathogenic· 221 VUS of 448 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SOX11

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.858

Z-score 2.76

OE 0.09 (0.03–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.26Z-score

OE missense 0.59 (0.52–0.68)

146 obs / 245.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.44)

0≤0.351.4

Missense OE?0.59 (0.52–0.68)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 1 / 10.8Missense obs/exp: 146 / 245.6Syn Z: -2.95

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSOX11-related neurodevelopmental disorderOTHERAD

This gene — mechanism propensity

0.2997th %ile

GOF

0.3193th %ile

LOF

0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 31% of P/LP variants are LoF · LOEUF 0.44 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFDeletion 2p25.2: a cryptic chromosome abnormality in a patient with autism and mental retardation detected using aCGH1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 18992374 ↗

ClinVar Variant Classifications

448 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22

Likely Pathogenic64

VUS221

Likely Benign92

Benign21

Conflicting27

Pathogenic

Likely Pathogenic

221

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	9	0	0	22
Likely Pathogenic	14	50	0	0	64
VUS	7	178	6	30	221
Likely Benign	0	23	2	67	92
Benign	0	10	3	8	21
Conflicting	—				27
Total	34	270	11	105	447

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

24 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap SOX11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →