GeneBe

AAGAB

protein-coding

alpha and gamma adaptin binding protein

Gene summary

The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

MANE transcript

NM_024666.5

Inheritance

AD

ClinVar variants

P:35U:77B:25

Top phenotype

Keratoderma, palmoplantar, punctate type IA

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr15:67,200,667-67,255,195

External References & Databases

Ensembl (ENSG00000103591)NCBI Gene (79719)OMIM (614888)HGNC:25662GenCCUniProt (Q6PD74)AlphaFoldClinVar (AAGAB)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~54.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

punctate palmoplantar keratoderma type 1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019332

Submitter: Orphanet

palmoplantar keratoderma, punctate type 1ASTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007858

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

palmoplantar keratoderma, punctate type 1ASTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007858

Submitter: Labcorp Genetics (formerly Invitae)

palmoplantar keratoderma, punctate type 1ASTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007858

Submitter: PanelApp Australia

palmoplantar keratoderma, punctate type 1ADEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007858

Submitter: Ambry Genetics

palmoplantar keratoderma, punctate type 1ASTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007858

Submitter: Genomics England PanelApp

palmoplantar keratoderma, punctate type 1ADEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007858

Submitter: G2P

Clinical Genomic Database (CGD)

Keratoderma, palmoplantar, punctate type IAAD

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 23000146; 23064416Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AAGAB variants in ClinVar

7 Conditions Cataloged
not specifiedTotal: 72
not providedTotal: 60
Palmoplantar keratoderma, punctate type 1ATotal: 18
AAGAB-related disorderTotal: 13
Palmoplantar keratodermasTotal: 1
Palmoplantar keratodermaTotal: 1
Neoplasm of the endocrine systemTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024666.5. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
9
clinvar
5
clinvar
 15
missense
74
clinvar
9
clinvar
2
clinvar
 85
nonsense
9
clinvar
1
clinvar
 10
start loss
1
clinvar
 1
frameshift
7
clinvar
7
clinvar
 14
splice donor/acceptor (+/-2bp)
3
clinvar
7
clinvar
2
clinvar
 12
Total191677187137

Highest pathogenic variant AF is 0.00007771186

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_024666.5RefSeqNP_078942.310MANE Select
ENST00000261880.10EnsemblENSP00000261880.510MANE Select
NM_001271885.2RefSeqNP_001258814.18Standard
NM_001271886.2RefSeqNP_001258815.18Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • protein transport

Molecular Function

  • protein binding

Cellular Component

  • cytoplasm
  • cytosol
  • nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000261880
Coding exons
10
Length
54163
Individuals with no LoFs
124757
Homozygous LoFs
0
Heterozygous LoFs
38
Defined
124795
p
0.000152
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.8771971651.190.000007732064
Missense (PolyPhen)7762.5631.2308816
Synonymous-0.5466660.61.090.00000301591
Loss of Function1.441319.90.6520.00000102223

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000260.00026rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000240.00023rare
South Asian0.0000340.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: May be involved in endocytic recycling of growth factor receptors such as EGFR. {ECO:0000269|PubMed:23064416}.;

Intolerance Scores

LoFtool
0.751
RVIS EVS
0.02
RVIS percentile EVS
55.61

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.965

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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