HYCC2

Chr 2AR

hyccin PI4KA lipid kinase complex subunit 2

Also known as: FAM126B

NCBI Gene: 285172 ENSG00000155744 UniProt: Q8IXS8 OMIM: 616797

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Predicted to be located in cytosol and membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.463 OMIM phenotypes

Clinical Summary— HYCC2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.179

Z-score 3.71

OE 0.25 (0.14–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.40Z-score

OE missense 0.77 (0.69–0.86)

224 obs / 291.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.14–0.46)

0≤0.351.4

Missense OE?0.77 (0.69–0.86)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 7 / 28.3Missense obs/exp: 224 / 291.0Syn Z: 1.34

This gene — mechanism propensity

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.