GSC2

Chr 22

goosecoid homeobox 2

Also known as: GSCL

GSC2 encodes a homeodomain-containing transcription factor that may regulate its own transcription and bind specific DNA sequences during development. The gene is located in the 22q11 deletion region associated with velocardiofacial syndrome and DiGeorge syndrome, which are characterized by conotruncal heart defects, craniofacial anomalies, and learning disabilities. These syndromes follow an autosomal dominant inheritance pattern due to hemizygous deletions, and the gene shows low constraint to loss-of-function variation in the general population.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.91
Clinical SummaryGSC2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.91LOEUF
pLI 0.004
Z-score -0.35
OE 1.24 (0.501.91)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.55Z-score
OE missense 1.20 (0.991.47)
69 obs / 57.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.24 (0.501.91)
00.351.4
Missense OE1.20 (0.991.47)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 3 / 2.4Missense obs/exp: 69 / 57.3Syn Z: 0.13
DN
0.6550th %ile
GOF
0.5562th %ile
LOF
0.57top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GSC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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