HMCN1
protein-codinghemicentin 1, the group of Fibulins|I-set domain containing
Gene summary
This gene encodes a large extracellular member of the immunoglobulin superfamily. A similar protein in C. elegans forms long, fine tracks at specific extracellular sites that are involved in many processes such as stabilization of the germline syncytium, anchorage of mechanosensory neurons to the epidermis, and organization of hemidesmosomes in the epidermis. Mutations in this gene may be associated with age-related macular degeneration. [provided by RefSeq, Jul 2008]
- ARMD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~456.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0011285
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0011285
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0011285
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Inheritance Pattern: AD
Disease ID:MONDO:0011285
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HMCN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031935.3. 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 | 46 | 774 | 24 | 844 | ||
| missense | 2047 | 163 | 16 | 2226 | ||
| nonsense | 28 | 28 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 30 | 1 | 32 | ||
| splice donor/acceptor (+/-2bp) | 38 | 2 | 40 | |||
| Total | 1 | 0 | 2189 | 940 | 40 | 3170 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_114141.2 | 107 | MANE Select | |
| Ensembl | ENSP00000271588.4 | 107 | MANE Select | |
| Ensembl | ENSP00000406205.1 | 6 | Standard | |
| Ensembl | ENSP00000698604.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hmcn1 | Danio rerio | Structure: dorsal fin Quality: has fewer parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell cycle
- homophilic cell adhesion via plasma membrane adhesion molecules
- heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
- visual perception
- response to bacterium
Molecular Function
- extracellular matrix structural constituent
- calcium ion binding
- signaling receptor activity
- protein homodimerization activity
- cell adhesion molecule binding
Cellular Component
- basement membrane
- cell-cell adherens junction
- cell cortex
- cleavage furrow
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000271588
- Coding exons
- 107
- Length
- 456403
- Individuals with no LoFs
- 125094
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 654
- Defined
- 125748
- p
- 0.00260
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.280 | 2910 | 2.95e+3 | 0.985 | 0.000157 | 36670 |
| Missense (PolyPhen) | 1519 | 1627.8 | 0.93314 | 20592 | ||
| Synonymous | -0.795 | 1094 | 1.06e+3 | 1.03 | 0.0000574 | 11224 |
| Loss of Function | 9.06 | 115 | 278 | 0.413 | 0.0000148 | 3404 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00099 | 0.00098 | rare |
| Latino/Admixed American | 0.0026 | 0.0026 | notable |
| Ashkenazi Jewish | 0.0025 | 0.0025 | notable |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0.0014 | 0.0014 | notable |
| European (Non-Finnish) | 0.0037 | 0.0036 | notable |
| South Asian | 0.0017 | 0.0017 | notable |
| Other | 0.0028 | 0.0028 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes cleavage furrow maturation during cytokinesis in preimplantation embryos. May play a role in the architecture of adhesive and flexible epithelial cell junctions. May play a role during myocardial remodeling by imparting an effect on cardiac fibroblast migration. {ECO:0000250|UniProtKB:D3YXG0}.;
Recessive Scores
- pRec
- 0.217
Intolerance Scores
- LoFtool
- 0.675
- RVIS EVS
- -3.69
- RVIS percentile EVS
- 0.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.604
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |