AKTIP

protein-coding

AKT interacting protein, the group of Ubiquitin conjugating enzymes E2|FHF complex

Gene summary

The mouse homolog of this gene produces fused toes and thymic hyperplasia in heterozygous mutant animals while homozygous mutants die in early development. This gene may play a role in apoptosis as these morphological abnormalities are caused by altered patterns of programmed cell death. The protein encoded by this gene is similar to the ubiquitin ligase domain of other ubiquitin-conjugating enzymes but lacks the conserved cysteine residue that enables those enzymes to conjugate ubiquitin to the target protein. This protein interacts directly with serine/threonine kinase protein kinase B (PKB)/Akt and modulates PKB activity by enhancing the phosphorylation of PKB's regulatory sites. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_022476.4

Inheritance

—

ClinVar variants

U:39B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr16:53,491,040-53,504,411

External References & Databases

Ensembl (ENSG00000166971)

Transcript & Mutation Effects

hg38 • Region Span ~13.4 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 AKTIP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022476.4. 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			2 clinvar			2
missense			37 clinvar	1 clinvar		38
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	39	1	0	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 90 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022476.4	RefSeq	NP_071921.1	9	MANE Select
ENST00000394657.12	Ensembl	ENSP00000378152.6	9	MANE Select
NM_001012398.3	RefSeq	NP_001012398.1	9	Standard
NM_001308325.2	RefSeq	NP_001295254.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of protein phosphorylation
apoptotic process
endosome organization
lysosome organization
endosome to lysosome transport

Molecular Function

protein binding
ubiquitin-like protein transferase activity

Cellular Component

cytosol
plasma membrane
HOPS complex
FHF complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394657
Coding exons: 9
Length: 13372
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.74	103	166	0.620	0.00000894	1908
Missense (PolyPhen)		15	44.471	0.3373		560
Synonymous	1.29	46	58.6	0.785	0.00000319	558
Loss of Function	3.08	4	18.1	0.220	9.50e-7	207

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). Regulates apoptosis by enhancing phosphorylation and activation of AKT1. Increases release of TNFSF6 via the AKT1/GSK3B/NFATC1 signaling cascade. {ECO:0000269|PubMed:14749367, ECO:0000269|PubMed:18799622}.;

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.285
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.900

Gene Damage Prediction

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