MORC4

Chr X

MORC family CW-type zinc finger 4

Also known as: ZCW4, ZCWCC2, dJ75H8.2

The MORC4 protein functions as a histone methylation reader that binds to various methylation states of histone H3 lysine 4, playing a role in chromatin regulation. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
14
P/LP submissions
0%
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryMORC4
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.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 74 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.998
Z-score 4.68
OE 0.10 (0.040.25)
Highly constrained

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

Missense Constraint
1.36Z-score
OE missense 0.79 (0.710.87)
260 obs / 329.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.040.25)
00.351.4
Missense OE0.79 (0.710.87)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 3 / 31.2Missense obs/exp: 260 / 329.6Syn Z: -0.90
DN
0.3793th %ile
GOF
0.3887th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.25

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

200 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS74
Likely Benign4
13
Pathogenic
1
Likely Pathogenic
74
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
72
2
0
74
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total07616092

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

View in ClinVar →

Protein Context — Lollipop Plot

MORC4 · 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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