HMCN2

protein-coding

hemicentin 2, the group of I-set domain containing|Fibulins

Gene summary

Predicted to enable axon guidance receptor activity. Predicted to be involved in homophilic cell-cell adhesion and synapse organization. Located in extracellular matrix. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001291815.2

Inheritance

—

ClinVar variants

U:1B:32

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr9:130,265,760-130,434,123

External References & Databases

Ensembl (ENSG00000148357)

Transcript & Mutation Effects

hg38 • Region Span ~168.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HMCN2 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 35

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001291815.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				28 clinvar		28
missense			1 clinvar	1 clinvar		2
nonsense						0
start loss						0
frameshift				2 clinvar		2
splice donor/acceptor (+/-2bp)				1 clinvar		1
Total	0	0	1	32	0	33

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001291815.2	RefSeq	NP_001278744.1	98	MANE Select
ENST00000683500.2	Ensembl	ENSP00000508292.2	98	MANE Select
ENST00000428715.2	Ensembl	ENSP00000387564.2	6	Standard
ENST00000487727.6	Ensembl	ENSP00000485578.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to stimulus

Molecular Function

extracellular matrix structural constituent
calcium ion binding

Cellular Component

basement membrane
extracellular space
cell cortex
cell junction
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000428715
Coding exons: 14
Length: 262629
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	368	430	0.855	0.0000284	5012
Missense (PolyPhen)		115	142.03	0.8097		1833
Synonymous	1.64	160	189	0.848	0.0000131	1646
Loss of Function	1.49	23	32.1	0.717	0.00000155	375

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Essentials

Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.158

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium