MAP4K5

protein-coding

mitogen-activated protein kinase kinase kinase kinase 5, the group of Mitogen-activated protein kinase kinase kinase kinases

Gene summary

This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006575.6

Inheritance

—

ClinVar variants

U:120B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr14:50,418,501-50,561,126

External References & Databases

Ensembl (ENSG00000012983)

Transcript & Mutation Effects

hg38 • Region Span ~142.6 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 MAP4K5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006575.6. 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		1 clinvar	3
missense			112 clinvar	3 clinvar		115
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	120	3	1	124

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006575.6	RefSeq	NP_006566.2	32	MANE Select
ENST00000682126.1	Ensembl	ENSP00000507200.1	32	MANE Select
NM_198794.4	RefSeq	NP_942089.1	32	Standard
ENST00000013125.10	Ensembl	ENSP00000013125.5	32	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-Core
Angiopoietin Like Protein 8 Regulatory Pathway
Insulin Signaling
mapkinase signaling pathway
EGFR1

Biological Process

activation of MAPKKK activity
protein phosphorylation
activation of JUN kinase activity
signal transduction by protein phosphorylation
stress-activated protein kinase signaling cascade

Molecular Function

protein kinase activity
protein serine/threonine kinase activity
protein binding
ATP binding
MAP kinase kinase kinase kinase activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000013125
Coding exons: 31
Length: 142626
Individuals with no LoFs: 124703
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 124717
p: 0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.06	268	381	0.703	0.0000179	5464
Missense (PolyPhen)		66	128.06	0.51539		1926
Synonymous	1.02	117	132	0.887	0.00000660	1501
Loss of Function	5.57	8	50.8	0.157	0.00000255	716

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000032	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.00018	0.00016	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. {ECO:0000269|PubMed:9038372}.;

Recessive Scores

pRec: 0.150

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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