RAB34

protein-coding

RAB34, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Gene summary

This gene encodes a protein belonging to the RAB family of proteins, which are small GTPases involved in protein transport. This family member is a Golgi-bound member of the secretory pathway that is involved in the repositioning of lysosomes and the activation of macropinocytosis. Alternative splicing of this gene results in multiple transcript variants. An alternatively spliced transcript variant produces the nine-amino acid residue-repeats (NARR) protein, which is a functionally distinct nucleolar protein resulting from a different reading frame. [provided by RefSeq, Dec 2016]

MANE transcript

NM_031934.6

Inheritance

ClinVar variants

P:4U:36B:3

Top phenotype

Orofaciodigital syndrome 20

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr17:28,714,281-28,718,429

External References & Databases

Ensembl (ENSG00000109113)

UniProt (P0DI83, Q9BZG1)

Transcript & Mutation Effects

hg38 • Region Span ~4.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

orofaciodigital syndrome 20STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0958230

Submitter: PanelApp Australia

orofaciodigital syndrome 20MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0958230

Submitter: G2P

Clinical Genomic Database (CGD)

Orofaciodigital syndrome 20AR

Manifestation: Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: Among other findings, the condition may include potentially occult cardiovascular and/or gastrointestinal anomalies, and awareness may enable surveillance, early diagnosis, and management

Refs: 37384395; 37619988

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAB34 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 31

Orofaciodigital syndrome 20Total: 7

Jeune thoracic dystrophyTotal: 2

RAB34-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031934.6. 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			2 clinvar	3 clinvar		5
missense	2 clinvar	1 clinvar	30 clinvar			33
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	2	2	36	3	0	43

Highest pathogenic variant AF is 0.000016728769

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 103 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031934.6	RefSeq	NP_114140.4	10	MANE Select
ENST00000395245.9	Ensembl	ENSP00000378666.3	10	MANE Select
NM_001142624.2	RefSeq	NP_001136096.2	11	Standard
NM_001142625.2	RefSeq	NP_001136097.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in squamous cell - TarBase

Biological Process

intracellular protein transport
endocytosis
antigen processing and presentation
cell projection organization
lysosome localization

Molecular Function

GTPase activity
protein binding
GTP binding
Ral GTPase binding
GTP-dependent protein binding

Cellular Component

Golgi apparatus
Golgi stack
cilium
phagocytic vesicle membrane
vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000447716
Coding exons: 11
Length: 4149
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	137	177	0.772	0.00000927	2045
Missense (PolyPhen)		57	77.777	0.73287		912
Synonymous	1.09	60	71.8	0.836	0.00000399	617
Loss of Function	1.56	13	20.7	0.629	0.00000124	207

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.968
RVIS EVS: -0.6
RVIS percentile EVS: 17.75

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.623

Gene Damage Prediction

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