HYCC2

Chr 2AR

hyccin PI4KA lipid kinase complex subunit 2

Also known as: FAM126B

NCBI Gene: 285172ENSG00000155744UniProt: Q8IXS8

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]

Primary Disease Associations & Inheritance

Gastrointestinal defects and immunodeficiency syndrome 2MIM #619708
AR
Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposisMIM #616531
AR
Spastic paraplegia 84, autosomal recessiveMIM #619621
AR
113
ClinVar variants
32
Pathogenic / LP
0.18
pLI score
0
Active trials
Clinical Summary— HYCC2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 62 VUS of 113 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.40Z-score
OE missense 0.77 (0.69–0.86)
224 obs / 291.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.14–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.69–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 7 / 28.3Missense obs/exp: 224 / 291.0Syn Z: 1.34

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS62
Likely Benign1
31
Pathogenic
1
Likely Pathogenic
62
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
57
5
0
62
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total05837095

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

View 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.

OMIM — Genotype-Phenotype Relationships

3 OMIM entries

OMIM
EFR3 HOMOLOG B; EFR3B
MIM #616797 · *

Gastrointestinal defects and immunodeficiency syndrome 2

MIM #619708

Molecular basis of disorder known

Autosomal recessive

Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

MIM #616531

Molecular basis of disorder known

Autosomal recessive

Spastic paraplegia 84, autosomal recessive

MIM #619621

Molecular basis of disorder known

Autosomal recessive
EFR3 HOMOLOG A; EFR3A
MIM #611798 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools