GPHN

Chr 14AR

gephyrin

Also known as: GEPH, GPH, GPHRYN, HKPX1, MOCODC

The protein anchors inhibitory glycine and GABA-A receptors to postsynaptic microtubules at inhibitory synapses and is required for molybdenum cofactor biosynthesis in non-neuronal tissues. Autosomal recessive loss-of-function mutations cause molybdenum cofactor deficiency type C and may be associated with hyperekplexia. The gene is highly intolerant to loss-of-function variants (pLI 0.999981), consistent with severe disease when both alleles are affected.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.181 OMIM phenotype
Clinical SummaryGPHN
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Gene-Disease Validity (ClinGen)
sulfite oxidase deficiency due to molybdenum cofactor deficiency type C · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 5.72
OE 0.07 (0.030.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.44Z-score
OE missense 0.54 (0.480.60)
239 obs / 442.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.030.18)
00.351.4
Missense OE0.54 (0.480.60)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 3 / 43.9Missense obs/exp: 239 / 442.9Syn Z: 0.21
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedGPHN-related molybdenum cofactor deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3495th %ile
GOF
0.4282th %ile
LOF
0.79top 5%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GPHN · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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