APCDD1

protein-coding

APC down-regulated 1

Gene summary

This locus encodes an inhibitor of the Wnt signaling pathway. Mutations at this locus have been associated with hereditary hypotrichosis simplex. Increased expression of this gene may also be associated with colorectal carcinogenesis.[provided by RefSeq, Sep 2010]

MANE transcript

NM_153000.5

Inheritance

ClinVar variants

P:1U:112B:37

Top phenotype

Hypotrichosis 1

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr18:10,454,635-10,489,949

External References & Databases

Ensembl (ENSG00000154856)

Transcript & Mutation Effects

hg38 • Region Span ~35.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypotrichosis 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011549

Submitter: PanelApp Australia

hypotrichosis 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011549

Submitter: G2P

hypotrichosis simplexSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018914

Submitter: Orphanet

hypotrichosis 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011549

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hypotrichosis 1AD

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: 10878665; 20393562; 22512811

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to APCDD1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 63

Hypotrichosis 1Total: 6

APCDD1-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153000.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				20 clinvar	8 clinvar	28
missense	1 clinvar		108 clinvar	6 clinvar	3 clinvar	118
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	0	112	26	11	150

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153000.5	RefSeq	NP_694545.1	5	MANE Select
ENST00000355285.10	Ensembl	ENSP00000347433.4	5	MANE Select
ENST00000423585.2	Ensembl	ENSP00000404930.2	2	Standard
ENST00000578882.1	Ensembl	ENSP00000463104.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

hair follicle development
Wnt signaling pathway
negative regulation of Wnt signaling pathway
astrocyte cell migration

Molecular Function

protein binding
Wnt-protein binding
identical protein binding

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355285
Coding exons: 5
Length: 35321
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.482	291	315	0.924	0.0000211	3369
Missense (PolyPhen)		120	129	0.93023		1373
Synonymous	-0.952	146	132	1.11	0.00000967	1025
Loss of Function	2.59	7	19.3	0.363	0.00000102	198

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negative regulator of the Wnt signaling pathway. Inhibits Wnt signaling in a cell-autonomous manner and functions upstream of beta-catenin. May act via its interaction with Wnt and LRP proteins. May play a role in colorectal tumorigenesis. {ECO:0000269|PubMed:12384519, ECO:0000269|PubMed:20393562}.;
Disease: DISEASE: Hypotrichosis 1 (HYPT1) [MIM:605389]: A rare form of non- syndromic hereditary hypotrichosis without characteristic hair shaft anomalies. Affected individuals typically show normal hair at birth, but hair loss and thinning of the hair shaft start during early childhood and progress with age. {ECO:0000269|PubMed:20393562}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.555
RVIS EVS: -1.37
RVIS percentile EVS: 4.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.301

Gene Damage Prediction

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