RHBDF1

protein-coding

rhomboid 5 homolog 1, the group of Rhomboid family

Gene summary

Predicted to enable growth factor binding activity and serine-type endopeptidase activity. Involved in several processes, including negative regulation of protein secretion; regulation of epidermal growth factor receptor signaling pathway; and regulation of proteasomal protein catabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C16orf8

MANE transcript

NM_022450.5

Inheritance

ClinVar variants

U:156B:14

Top phenotype

Wolff-Parkinson-White pattern

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr16:58,059-76,355

External References & Databases

Ensembl (ENSG00000007384)

Transcript & Mutation Effects

hg38 • Region Span ~18.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dilated cardiomyopathyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005021

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RHBDF1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 143

not providedTotal: 12

Wolff-Parkinson-White patternTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022450.5. 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			1 clinvar	4 clinvar	5 clinvar	10
missense			151 clinvar	3 clinvar	2 clinvar	156
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	156	7	7	170

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 87 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022450.5	RefSeq	NP_071895.3	17	MANE Select
ENST00000262316.10	Ensembl	ENSP00000262316.5	17	MANE Select
ENST00000417043.5	Ensembl	ENSP00000412218.1	3	Standard
ENST00000419764.1	Ensembl	ENSP00000394427.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
cell population proliferation
protein transport
cell migration
regulation of epidermal growth factor receptor signaling pathway

Molecular Function

serine-type endopeptidase activity
growth factor binding

Cellular Component

Golgi membrane
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262316
Coding exons: 17
Length: 18297
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125748
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.45	481	579	0.830	0.0000416	5532
Missense (PolyPhen)		181	227.53	0.79551		2178
Synonymous	-0.0322	243	242	1.00	0.0000180	1703
Loss of Function	1.89	29	42.3	0.686	0.00000220	429

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00032	0.00031	rare
South Asian	0.00033	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Rhomboid protease-like protein which has no protease activity but regulates the secretion of several ligands of the epidermal growth factor receptor. Indirectly activates the epidermal growth factor receptor signaling pathway and may thereby regulate sleep, cell survival, proliferation and migration. {ECO:0000269|PubMed:15965977, ECO:0000269|PubMed:18524845, ECO:0000269|PubMed:18832597, ECO:0000269|PubMed:21439629}.;

Intolerance Scores

RVIS EVS: -0.79
RVIS percentile EVS: 12.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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