ASIP

agouti signaling protein

Basic information

Region (hg38): 20:34194569-34269344

Previous symbols: [ "AGTIL" ]

Links

ENSG00000101440 ∙ NCBI:434 ∙ OMIM:600201 ∙ HGNC:745 ∙ Uniprot:P42127 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Obesity and hypopigmentation; Skin/hair/eye pigmentation 9	AD	General	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	Dermatologic; Endocrine	11833005; 18488028; 36536132

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASIP gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASIP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			6	1		7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	1	1

Variants in ASIP

This is a list of pathogenic ClinVar variants found in the ASIP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-34260490-A-T		not specified • ASIP-related condition	Uncertain significance (Jan 17, 2024)
20-34260491-C-T		ASIP-related condition	Likely benign (Aug 29, 2024)
20-34260498-G-T		not specified	Uncertain significance (Aug 10, 2021)
20-34260508-T-C		not specified	Uncertain significance (Jun 11, 2021)
20-34262852-C-A		not specified	Likely benign (Oct 26, 2022)
20-34262856-T-A		not specified	Uncertain significance (Feb 05, 2024)
20-34262857-C-T		ASIP-related condition	Likely benign (Jul 18, 2024)
20-34262885-T-C		ASIP-related condition	Uncertain significance (Sep 06, 2024)
20-34268987-G-A		ASIP-related condition	Likely benign (Sep 04, 2024)
20-34268991-A-G		not specified	Uncertain significance (Dec 13, 2022)
20-34269013-T-C		not specified	Uncertain significance (Mar 29, 2024)
20-34269032-C-A		ASIP-related condition	Benign (Jun 04, 2018)
20-34269032-C-G		ASIP-related condition	Likely benign (Aug 23, 2024)
20-34269065-C-G		not specified	Uncertain significance (Dec 12, 2023)
20-34269125-C-T		ASIP-related condition	Likely benign (Jul 21, 2024)
20-34269192-A-G		SKIN/HAIR/EYE PIGMENTATION 9, DARK/LIGHT HAIR	association (Jul 26, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASIP	protein_coding	protein_coding	ENST00000568305	3	74776

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0163	0.721	125736	0	11	125747	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.119	77	80.0	0.962	0.00000481	844
Missense in Polyphen		37	39.827	0.92902		424
Synonymous	0.734	27	32.3	0.836	0.00000185	270
Loss of Function	0.708	3	4.65	0.646	2.81e-7	53

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000503	0.0000462
European (Non-Finnish)	0.0000569	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000331	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the regulation of melanogenesis. The binding of ASP to MC1R precludes alpha-MSH initiated signaling and thus blocks production of cAMP, leading to a down-regulation of eumelanogenesis (brown/black pigment) and thus increasing synthesis of pheomelanin (yellow/red pigment). In higher primates, agouti may affect the quality of hair pigmentation rather than its pattern of deposition. Could well play a role in neuroendocrine aspects of melanocortin action. May have some functional role in regulating the lipid metabolism with adipocytes.
• Pathway: Melanogenesis - Homo sapiens (human);Adipogenesis;Insulin-mediated glucose transport (Consensus)

Haploinsufficiency Scores

• pHI: 0.467
• hipred: N
• hipred_score: 0.199
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.141

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: a
• Phenotype: hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); pigmentation phenotype; neoplasm; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: asip2b
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: dispersed

Gene ontology

• Biological process: generation of precursor metabolites and energy;signal transduction;cell-cell signaling;adult feeding behavior;hormone-mediated signaling pathway;melanosome transport;melanosome organization;regulation of molecular function, epigenetic;melanin biosynthetic process;positive regulation of melanin biosynthetic process;genetic imprinting
• Cellular component: extracellular space;cell
• Molecular function: signaling receptor binding;type 3 melanocortin receptor binding;type 4 melanocortin receptor binding