RHBDF2

rhomboid 5 homolog 2, the group of Rhomboid family

Basic information

Region (hg38): 17:76470891-76501790

Previous symbols: [ "RHBDL6", "TOC" ]

Links

ENSG00000129667

∙ NCBI:79651 ∙ OMIM:614404 ∙ HGNC:20788 ∙ Uniprot:Q6PJF5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

palmoplantar keratoderma-esophageal carcinoma syndrome (Strong), mode of inheritance: AD
palmoplantar keratoderma-esophageal carcinoma syndrome (Strong), mode of inheritance: AD
palmoplantar keratoderma-esophageal carcinoma syndrome (Supportive), mode of inheritance: AD
palmoplantar keratoderma-esophageal carcinoma syndrome (Moderate), mode of inheritance: AD
palmoplantar keratoderma-esophageal carcinoma syndrome (Definitive), mode of inheritance: AD
palmoplantar keratoderma-esophageal carcinoma syndrome (Definitive), mode of inheritance: AD
palmoplantar keratoderma-esophageal carcinoma syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tylosis with esophageal cancer	AD	Oncologic	Surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Individuals may be at especially high risk of esophageal cancer with tobacco use	Dermatologic; Gastrointestinal; Oncologic	13209063; 8508402; 8666405; 8651714; 22265016

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RHBDF2 gene.

Palmoplantar_keratoderma-esophageal_carcinoma_syndrome (216 variants)
not_provided (213 variants)
Inborn_genetic_diseases (118 variants)
RHBDF2-related_disorder (14 variants)
not_specified (6 variants)
Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHBDF2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001005498.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	51 clinvar	5 clinvar	64
missense		2 clinvar	239 clinvar	40 clinvar	3 clinvar	284
nonsense						0
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)						0
Total	0	2	251	91	8

Highest pathogenic variant AF is 0.0000020665

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RHBDF2	protein_coding	protein_coding	ENST00000313080	17	30900

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00119	0.999	125714	0	32	125746	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.79	432	550	0.785	0.0000371	5505
Missense in Polyphen		148	228.83	0.64676		2302
Synonymous	0.742	215	229	0.938	0.0000157	1674
Loss of Function	4.04	13	40.9	0.318	0.00000200	430

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000483	0.000474
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000143	0.000139
European (Non-Finnish)	0.0000720	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

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 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

loftool: 0.756
rvis_EVS: -0.37
rvis_percentile_EVS: 28.29

Haploinsufficiency Scores

pHI: 0.228
hipred: Y
hipred_score: 0.639
ghis: 0.549

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.650

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Rhbdf2
Phenotype: liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; cellular phenotype; skeleton phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: proteolysis;protein transport;regulation of epidermal growth factor receptor signaling pathway;regulation of protein secretion;negative regulation of protein secretion
Cellular component: endoplasmic reticulum membrane;plasma membrane;integral component of membrane
Molecular function: serine-type endopeptidase activity;growth factor binding