GEMIN4

Chr 17

gem nuclear organelle associated protein 4

Also known as: HC56, HCAP1, HHRF-1, NEDMCR, p97

The GEMIN4 protein is part of the SMN complex that catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), which are essential building blocks of the spliceosome required for pre-mRNA splicing. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities. The gene is extremely intolerant to loss-of-function variants (pLI near 1), indicating that heterozygous loss alone would be detrimental, consistent with the recessive inheritance pattern where complete loss of function requires variants in both alleles.

ResearchSummary from RefSeq, OMIM, UniProt
LOEUF 1.01
Clinical SummaryGEMIN4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 267 VUS of 416 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.52
OE 0.72 (0.521.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.47Z-score
OE missense 1.05 (0.991.13)
626 obs / 593.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.72 (0.521.01)
00.351.4
Missense OE1.05 (0.991.13)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 24 / 33.5Missense obs/exp: 626 / 593.9Syn Z: -1.37

ClinVar Variant Classifications

416 submitted variants in ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic8
VUS267
Likely Benign55
Benign23
Conflicting6
55
Pathogenic
8
Likely Pathogenic
267
VUS
55
Likely Benign
23
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
54
0
55
Likely Pathogenic
1
1
6
0
8
VUS
10
206
51
0
267
Likely Benign
0
21
2
32
55
Benign
0
15
1
7
23
Conflicting
6
Total1124411439414

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

View in ClinVar →

Protein Context — Lollipop Plot

GEMIN4 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC