APLP1

protein-coding

amyloid beta precursor like protein 1

Gene summary

This gene encodes a member of the highly conserved amyloid precursor protein gene family. The encoded protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor protein cleavage. This cleavage liberates an intracellular cytoplasmic fragment that may act as a transcriptional activator. The encoded protein may also play a role in synaptic maturation during cortical development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001024807.3

Inheritance

—

ClinVar variants

U:95B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr19:35,867,899-35,879,803

External References & Databases

Ensembl (ENSG00000105290)

Transcript & Mutation Effects

hg38 • Region Span ~11.9 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 APLP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 87

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001024807.3. 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			4 clinvar		1 clinvar	5
missense			86 clinvar	5 clinvar		91
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	95	5	1	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001024807.3	RefSeq	NP_001019978.1	17	MANE Select
ENST00000221891.9	Ensembl	ENSP00000221891.4	17	MANE Select
NM_005166.5	RefSeq	NP_005157.1	17	Standard
ENST00000537454.6	Ensembl	ENSP00000441501.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endocytosis
apoptotic process
cell adhesion
nervous system development
animal organ morphogenesis

Molecular Function

protein binding
heparin binding
alpha-2A adrenergic receptor binding
alpha-2B adrenergic receptor binding
alpha-2C adrenergic receptor binding

Cellular Component

basement membrane
plasma membrane
integral component of membrane
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000221891
Coding exons: 17
Length: 11893
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125747
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	324	392	0.828	0.0000246	4157
Missense (PolyPhen)		137	179.06	0.76512		1941
Synonymous	-1.17	177	158	1.12	0.0000101	1348
Loss of Function	4.17	9	36.0	0.250	0.00000188	374

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in postsynaptic function. The C-terminal gamma-secretase processed fragment, ALID1, activates transcription activation through APBB1 (Fe65) binding (By similarity). Couples to JIP signal transduction through C-terminal binding. May interact with cellular G-protein signaling pathways. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. {ECO:0000250}.;

Recessive Scores

pRec: 0.617

Intolerance Scores

LoFtool: 0.0546
RVIS EVS: -0.68
RVIS percentile EVS: 15.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.760

Gene Damage Prediction

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