GPKOW

Chr X

G-patch domain and KOW motifs

Also known as: GPATC5, GPATCH5, Mos2, Spp2, T54

The protein is an RNA-binding component of the minor spliceosome that splices U12-type introns in pre-mRNAs and interacts with protein kinases A and X. Mutations cause X-linked intellectual disability with microcephaly and seizures. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.19
Clinical SummaryGPKOW
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Gene-Disease Validity (ClinGen)
holoprosencephaly-hypokinesia-congenital contractures syndrome · XLModerate

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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ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 66 VUS of 203 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 0.996
Z-score 3.71
OE 0.00 (0.000.19)
Highly constrained

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

Missense Constraint
0.92Z-score
OE missense 0.82 (0.720.93)
166 obs / 202.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.19)
00.351.4
Missense OE0.82 (0.720.93)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 0 / 16.0Missense obs/exp: 166 / 202.9Syn Z: -0.23
DN
0.3395th %ile
GOF
0.3193th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.19

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

203 submitted variants in ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic2
VUS66
Likely Benign8
Benign5
Conflicting1
57
Pathogenic
2
Likely Pathogenic
66
VUS
8
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
57
0
57
Likely Pathogenic
0
0
2
0
2
VUS
1
55
9
1
66
Likely Benign
0
5
1
2
8
Benign
0
1
2
2
5
Conflicting
1
Total161715139

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

View in ClinVar →

Protein Context — Lollipop Plot

GPKOW · 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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