HYCC1

Chr 7AR

hyccin PI4KA lipid kinase complex subunit 1

Also known as: DRCTNNB1A, FAM126A, HCC, HLD5

The protein is a component of a complex that localizes phosphatidylinositol 4-kinase to the plasma membrane and regulates phosphatidylinositol 4-phosphate synthesis, playing a key role in oligodendrocyte formation and myelination of the central and peripheral nervous systems. Mutations cause leukodystrophy, hypomyelinating, 5 (also known as hypomyelination with congenital cataract), which follows autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.485), and the congenital onset is reflected in the phenotype name.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.481 OMIM phenotype
Clinical SummaryHYCC1
🧬
Gene-Disease Validity (ClinGen)
hypomyelinating leukodystrophy 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
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ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 199 VUS of 436 total submissions
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GeneReview available — HYCC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.121
Z-score 3.58
OE 0.26 (0.150.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.98Z-score
OE missense 0.83 (0.740.93)
224 obs / 269.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.150.48)
00.351.4
Missense OE0.83 (0.740.93)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 7 / 27.1Missense obs/exp: 224 / 269.3Syn Z: -1.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHYCC1-related leukodystrophy, hypomyelinatingLOFAR

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

DN
0.6649th %ile
GOF
0.6930th %ile
LOF
0.4628th %ile

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

436 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic16
VUS199
Likely Benign121
Benign40
Conflicting13
36
Pathogenic
16
Likely Pathogenic
199
VUS
121
Likely Benign
40
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
29
0
36
Likely Pathogenic
14
0
2
0
16
VUS
3
119
73
4
199
Likely Benign
0
11
43
67
121
Benign
0
1
35
4
40
Conflicting
13
Total2313218275425

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

View in ClinVar →

Protein Context — Lollipop Plot

HYCC1 · 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
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found