RBSN

protein-coding

rabenosyn, RAB effector, the group of Zinc fingers FYVE-type

Gene summary

This gene encodes a protein that belongs to the FYVE zinc finger family of proteins. The encoded protein interacts with Ras-related proteins that regulate membrane trafficking. A missense mutation in this gene is associated with a defect in the early endocytic pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Previous symbols:

ZFYVE20

MANE transcript

NM_022340.4

Inheritance

ClinVar variants

P:3U:114B:13

Top phenotype

Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr3:15,070,069-15,099,163

External References & Databases

Ensembl (ENSG00000131381)

Transcript & Mutation Effects

hg38 • Region Span ~29.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Kariminejad neurodevelopmental syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0975795

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities AR

Manifestation: Craniofacial; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Hematologic

Rationale: Individuals may be affected by hematologic abnormalities, including anemia, thrombocytopenia, neutropenia, and myelofibrosis, and awareness may allow early diagnosis and management; HSCT has been described

Refs: 29784638; 35652444

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RBSN variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 14

Kariminejad neurodevelopmental syndromeTotal: 3

Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalitiesTotal: 2

RBSN-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022340.4. 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				4 clinvar	4 clinvar	8
missense	3 clinvar		111 clinvar	5 clinvar		119
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	3	0	114	9	4	130

Highest pathogenic variant AF is 0.0000034203376

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022340.4	RefSeq	NP_071735.2	11	MANE Select
ENST00000253699.7	Ensembl	ENSP00000253699.3	11	MANE Select
NM_001302378.2	RefSeq	NP_001289307.1	11	Standard
ENST00000426541.1	Ensembl	ENSP00000403368.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Toll Like Receptor 9 (TLR9) Cascade
Toll-Like Receptors Cascades
Factors involved in megakaryocyte development and platelet production
Innate Immune System

Biological Process

blood coagulation
protein transport
endosomal transport
early endosome to Golgi transport
Golgi to lysosome transport

Molecular Function

nucleic acid binding
protein binding
zinc ion binding
Rab GTPase binding

Cellular Component

endosome
cytosol
plasma membrane
endosome membrane
early endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253699
Coding exons: 11
Length: 29091
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.37	370	452	0.818	0.0000266	5145
Missense (PolyPhen)		107	135.95	0.78706		1553
Synonymous	1.61	145	172	0.844	0.00000949	1524
Loss of Function	4.25	11	40.0	0.275	0.00000244	430

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
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: Rab4/Rab5 effector protein acting in early endocytic membrane fusion and membrane trafficking of recycling endosomes. Required for endosome fusion either homotypically or with clathrin coated vesicles. Plays a role in the lysosomal trafficking of CTSD/cathepsin D from the Golgi to lysosomes. Also promotes the recycling of transferrin directly from early endosomes to the plasma membrane. Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate (PtdInsP3) (PubMed:11062261, PubMed:11788822, PubMed:15020713). Plays a role in the recycling of transferrin receptor to the plasma membrane (PubMed:22308388). {ECO:0000269|PubMed:11062261, ECO:0000269|PubMed:11788822, ECO:0000269|PubMed:15020713, ECO:0000269|PubMed:22308388}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

RVIS EVS: -0.42
RVIS percentile EVS: 25.73

Essentials

Essential (gene trap): N