RHBDL3

protein-coding

rhomboid like 3, the group of EF-hand domain containing|Rhomboid family

Gene summary

Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

RHBDL4

MANE transcript

NM_138328.3

Inheritance

—

ClinVar variants

U:60B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr17:32,265,832-32,324,659

External References & Databases

Ensembl (ENSG00000141314)

Transcript & Mutation Effects

hg38 • Region Span ~58.8 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 RHBDL3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138328.3. 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						0
missense			59 clinvar	2 clinvar		61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	60	2	0	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138328.3	RefSeq	NP_612201.1	9	MANE Select
ENST00000269051.9	Ensembl	ENSP00000269051.4	9	MANE Select
NM_001330181.2	RefSeq	NP_001317110.1	8	Standard
NM_001363834.1	RefSeq	NP_001350763.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

serine-type endopeptidase activity
calcium ion binding

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269051
Coding exons: 9
Length: 58486
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.627	208	235	0.885	0.0000144	2600
Missense (PolyPhen)		92	111.07	0.82834		1131
Synonymous	1.03	89	102	0.870	0.00000668	847
Loss of Function	1.40	14	20.9	0.669	0.00000116	212

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. {ECO:0000250}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.633
RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0839

Gene Damage Prediction

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