AFAP1L2

protein-coding

actin filament associated protein 1 like 2, the group of Pleckstrin homology domain containing

Gene summary

Enables SH2 domain binding activity; SH3 domain binding activity; and protein tyrosine kinase activator activity. Involved in several processes, including positive regulation of epidermal growth factor receptor signaling pathway; regulation of gene expression; and regulation of mitotic cell cycle. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

KIAA1914

MANE transcript

NM_001001936.3

Inheritance

—

ClinVar variants

U:132B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr10:114,294,824-114,404,756

External References & Databases

Ensembl (ENSG00000169129)

Transcript & Mutation Effects

hg38 • Region Span ~109.9 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 AFAP1L2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 126

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001001936.3. 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	4 clinvar	1 clinvar	7
missense			126 clinvar	6 clinvar		132
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	132	10	1	143

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 93 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001001936.3	RefSeq	NP_001001936.1	19	MANE Select
ENST00000304129.9	Ensembl	ENSP00000303042.4	19	MANE Select
NM_001287824.2	RefSeq	NP_001274753.1	20	Standard
NM_001351064.2	RefSeq	NP_001337993.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1

Biological Process

inflammatory response
regulation of mitotic cell cycle
regulation of interleukin-6 production
positive regulation of interleukin-8 production
positive regulation of epidermal growth factor receptor signaling pathway

Molecular Function

SH3 domain binding
protein tyrosine kinase activator activity
signaling adaptor activity
SH2 domain binding

Cellular Component

cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304129
Coding exons: 19
Length: 109933
Individuals with no LoFs: 125699
Homozygous LoFs: 1
Heterozygous LoFs: 48
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.654	429	469	0.915	0.0000273	5321
Missense (PolyPhen)		123	141.12	0.87159		1670
Synonymous	-0.0213	201	201	1.00	0.0000128	1589
Loss of Function	4.19	13	42.5	0.306	0.00000199	516

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00039	0.00036	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation. {ECO:0000269|PubMed:17412687}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.636
RVIS EVS: 0.79
RVIS percentile EVS: 87.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.196

Gene Damage Prediction

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