HMCN1

hemicentin 1, the group of Fibulins|I-set domain containing

Basic information

Region (hg38): 1:185734390-186190949

Previous symbols: [ "ARMD1" ]

Links

ENSG00000143341 ∙ NCBI:83872 ∙ OMIM:608548 ∙ HGNC:19194 ∙ Uniprot:Q96RW7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• age related macular degeneration 1 (Limited), mode of inheritance: AD
• age related macular degeneration 1 (Limited), mode of inheritance: AD
• age related macular degeneration 1 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macular degeneration, age-related, 1	AD	General	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	Ophthalmologic	16020313; 17216616; 25986072

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HMCN1 gene.

• not provided (2202 variants)
• Age related macular degeneration 1 (474 variants)
• Inborn genetic diseases (224 variants)
• Macular degeneration (15 variants)
• not specified (7 variants)
• HMCN1-related condition (2 variants)
• MACULAR DEGENERATION, AGE-RELATED, 1, SUSCEPTIBILITY TO (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HMCN1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			39	433	33	505
missense			1228	74	31	1333
nonsense			16			16
start loss						0
frameshift			17			17
inframe indel			5			5
splice donor/acceptor (+/-2bp)			13	4		17
splice region			58	79	14	151
non coding			44	204	35	283
Total	0	0	1362	715	99

Variants in HMCN1

This is a list of pathogenic ClinVar variants found in the HMCN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-185734624-G-A		Age related macular degeneration 1	Uncertain significance (Jan 12, 2018)
1-185734629-C-A		Age related macular degeneration 1	Uncertain significance (Jan 12, 2018)
1-185734659-A-G		Age related macular degeneration 1	Uncertain significance (Jan 12, 2018)
1-185734693-T-C		Age related macular degeneration 1	Uncertain significance (Jan 13, 2018)
1-185734740-T-C		Age related macular degeneration 1	Uncertain significance (Jan 13, 2018)
1-185734750-A-AG		Macular degeneration	Uncertain significance (Jun 14, 2016)
1-185734762-A-AG		Macular degeneration	Uncertain significance (Jun 14, 2016)
1-185734774-AAG-A		HMCN1-related disorder	Likely benign (Aug 01, 2019)
1-185734787-C-A			Uncertain significance (Jun 04, 2022)
1-185734795-G-A			Uncertain significance (Aug 25, 2023)
1-185734802-A-T			Uncertain significance (Dec 24, 2023)
1-185734805-C-T			Uncertain significance (Jan 02, 2024)
1-185734809-A-G			Likely benign (Oct 05, 2022)
1-185734815-G-C		Age related macular degeneration 1 • HMCN1-related disorder	Benign/Likely benign (Jan 04, 2024)
1-185734829-A-T			Uncertain significance (Dec 14, 2023)
1-185734833-T-C			Likely benign (May 21, 2022)
1-185734836-C-T		Age related macular degeneration 1	Benign (Jan 25, 2024)
1-185734837-C-T			Likely benign (Sep 21, 2023)
1-185734838-T-C			Uncertain significance (Nov 08, 2022)
1-185734841-C-T		not specified	Uncertain significance (May 08, 2023)
1-185734842-T-A			Likely benign (Sep 13, 2022)
1-185734842-T-C			Likely benign (Aug 28, 2023)
1-185734855-C-T			Uncertain significance (Sep 21, 2023)
1-185734858-C-G			Uncertain significance (May 05, 2023)
1-185734868-T-A			Uncertain significance (Sep 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HMCN1	protein_coding	protein_coding	ENST00000271588	107	456403

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.63e-38	1.00	125094	0	654	125748	0.00260

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.280	2910	2.95e+3	0.985	0.000157	36670
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00357	0.00357
Ashkenazi Jewish	0.00249	0.00248
East Asian	0.000599	0.000598
Finnish	0.00144	0.00143
European (Non-Finnish)	0.00365	0.00363
Middle Eastern	0.000599	0.000598
South Asian	0.00174	0.00173
Other	0.00279	0.00277

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.117
• hipred: N
• hipred_score: 0.492
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.604

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hmcn1

Zebrafish Information Network

• Gene name: hmcn1
• Affected structure: dorsal fin
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• 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;cell division
• Cellular component: basement membrane;cell-cell adherens junction;cell cortex;cleavage furrow;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent;calcium ion binding;signaling receptor activity;protein homodimerization activity;cell adhesion molecule binding