HORMAD1

protein-coding

HORMA domain containing 1

Gene summary

This gene encodes a HORMA domain-containing protein. HORMA domains are involved in chromatin binding and play a role in cell cycle regulation. The encoded protein may play a role in meiosis, and expression of this gene is a potential marker for cancer. A pseudogene of this gene is located on the long arm of chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

MANE transcript

NM_032132.5

Inheritance

ClinVar variants

P:1U:33B:4

Top phenotype

Male infertility

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr1:150,698,060-150,720,895

External References & Databases

Ensembl (ENSG00000143452)

Transcript & Mutation Effects

hg38 • Region Span ~22.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0018393

Submitter: King Faisal Specialist Hospital and Research Center

Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate with total score of 8. Single-variant analysis (3 points), experimental evidence: Animal model (4 points) and testicular expression (1 points) (PMID: 21478856; PMID: 21079677).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HORMAD1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 2

Male infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032132.5. 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						0
missense			30 clinvar	3 clinvar	1 clinvar	34
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	33	3	1	38

Highest pathogenic variant AF is 7.1850644e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032132.5	RefSeq	NP_115508.2	14	MANE Select
ENST00000361824.7	Ensembl	ENSP00000355167.2	14	MANE Select
NM_001199829.2	RefSeq	NP_001186758.1	13	Standard
ENST00000322343.11	Ensembl	ENSP00000326489.7	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

blastocyst development
synaptonemal complex assembly
spermatogenesis
meiotic DNA double-strand break formation
oogenesis

Cellular Component

synaptonemal complex
nucleus
chromosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361824
Coding exons: 14
Length: 22829
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125726
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.54	132	192	0.688	0.00000886	2600
Missense (PolyPhen)		31	68.238	0.45429		890
Synonymous	0.717	56	63.3	0.885	0.00000309	677
Loss of Function	3.82	3	22.6	0.133	0.00000105	312

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000096	0.000092	rare
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a key role in meiotic progression. Regulates 3 different functions during meiosis: ensures that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends. Promotes synaptonemal-complex formation independently of its role in homology search. Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes. {ECO:0000250|UniProtKB:Q9D5T7}.;

Recessive Scores

pRec: 0.0994

Intolerance Scores

LoFtool: 0.789
RVIS EVS: 0.1
RVIS percentile EVS: 61.49

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0770

Gene Damage Prediction

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