The protein enables axon guidance receptor activity and is involved in homophilic cell adhesion via plasma membrane adhesion molecules and synapse organization within the collagen-containing extracellular matrix. Mutations cause disease through a dominant-negative mechanism. The inheritance pattern and specific associated diseases are not established in the current literature.

OMIMResearchSummary from RefSeq, Mechanism
DNmechanismLOEUF 1.01
Clinical SummaryHMCN2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.49
OE 0.72 (0.521.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.07Z-score
OE missense 0.86 (0.780.93)
368 obs / 430.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.521.01)
00.351.4
Missense OE0.86 (0.780.93)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 23 / 32.1Missense obs/exp: 368 / 430.3Syn Z: 1.64
DN
0.6841th %ile
GOF
0.5856th %ile
LOF
0.3941th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

HMCN2 · 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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