HYCC2

Chr 2AR

hyccin PI4KA lipid kinase complex subunit 2

Also known as: FAM126B

The protein is a component of a complex that localizes phosphatidylinositol 4-kinase to the plasma membrane, where it functions in phospholipid biosynthesis. The gene is highly constrained against loss-of-function variants (LOEUF 0.464), but no established human diseases have been definitively linked to HYCC2 mutations. Clinical significance of variants in this gene remains uncertain pending further research.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismARLOEUF 0.464 OMIM phenotypes
Clinical SummaryHYCC2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.179
Z-score 3.71
OE 0.25 (0.140.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.40Z-score
OE missense 0.77 (0.690.86)
224 obs / 291.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.140.46)
00.351.4
Missense OE0.77 (0.690.86)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 7 / 28.3Missense obs/exp: 224 / 291.0Syn Z: 1.34
DN
0.6455th %ile
GOF
0.7126th %ile
LOF
0.4825th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HYCC2 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found