R3HDML

protein-coding

R3H domain containing like, the group of CAP superfamily

Gene summary

Predicted to enable peptidase inhibitor activity. Predicted to be located in extracellular region. Predicted to be active in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_178491.4

Inheritance

—

ClinVar variants

U:37B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr20:44,337,043-44,351,238

External References & Databases

Ensembl (ENSG00000101074)

Transcript & Mutation Effects

hg38 • Region Span ~14.2 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 R3HDML variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 41

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178491.4. 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			37 clinvar	4 clinvar		41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	37	4	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178491.4	RefSeq	NP_848586.1	5	MANE Select
ENST00000217043.4	Ensembl	ENSP00000217043.3	5	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of peptidase activity

Molecular Function

peptidase inhibitor activity

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217043
Coding exons: 5
Length: 14250
Individuals with no LoFs: 125272
Homozygous LoFs: 0
Heterozygous LoFs: 476
Defined: 125748
p: 0.00189

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.545	144	164	0.880	0.00000994	1658
Missense (PolyPhen)		38	45.844	0.82889		494
Synonymous	-0.475	71	66.1	1.07	0.00000421	486
Loss of Function	0.653	10	12.5	0.801	5.35e-7	129

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.0018	0.0018	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.0012	0.0012	notable
European (Non-Finnish)	0.0032	0.0032	notable
South Asian	0.00013	0.00013	rare
Other	0.0021	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative serine protease inhibitor. {ECO:0000250}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.759
RVIS EVS: 0.71
RVIS percentile EVS: 85.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0803

Gene Damage Prediction

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