CYTH4

protein-coding

cytohesin 4, the group of Pleckstrin homology domain containing|Cytohesins

Gene summary

This gene encodes a member of the PSCD family of proteins, which have an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family function as GEPs for ADP-ribosylation factors (ARFs), which are guanine nucleotide-binding proteins involved in vesicular trafficking pathways. This protein exhibits GEP activity in vitro with ARF1 and ARF5, but is inactive with ARF6. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

Previous symbols:

PSCD4

MANE transcript

NM_013385.5

Inheritance

—

ClinVar variants

U:50B:6

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr22:37,282,027-37,315,341

External References & Databases

Ensembl (ENSG00000100055)

Transcript & Mutation Effects

hg38 • Region Span ~33.3 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 CYTH4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 52

not providedTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013385.5. 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		1 clinvar	2
missense			49 clinvar	3 clinvar	2 clinvar	54
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	3	3	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013385.5	RefSeq	NP_037517.1	13	MANE Select
ENST00000248901.11	Ensembl	ENSP00000248901.6	13	MANE Select
NM_001318024.2	RefSeq	NP_001304953.1	10	Standard
ENST00000402997.5	Ensembl	ENSP00000385997.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Phospholipase D signaling pathway - Homo sapiens (human)
Vesicle-mediated transport
thrombin signaling and protease-activated receptors
Membrane Trafficking

Biological Process

regulation of ARF protein signal transduction

Molecular Function

ARF guanyl-nucleotide exchange factor activity
lipid binding

Cellular Component

Golgi membrane
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000248901
Coding exons: 13
Length: 33315
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.43	199	264	0.753	0.0000178	2628
Missense (PolyPhen)		62	110.21	0.56255		1069
Synonymous	0.961	95	108	0.882	0.00000790	709
Loss of Function	2.97	10	26.5	0.378	0.00000145	270

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes guanine-nucleotide exchange on ARF1 and ARF5. Promotes the activation of ARF factors through replacement of GDP with GTP. {ECO:0000269|PubMed:10652308}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.543
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.885

Gene Damage Prediction

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