KITLG

KIT ligand

Basic information

Region (hg38): 12:88492793-88580851

Previous symbols: [ "MGF" ]

Links

ENSG00000049130 ∙ NCBI:4254 ∙ OMIM:184745 ∙ HGNC:6343 ∙ Uniprot:P21583 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 69 (Moderate), mode of inheritance: AD
• Waardenburg syndrome type 2 (Supportive), mode of inheritance: AD
• familial progressive hyperpigmentation (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• familial progressive hyper- and hypopigmentation (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 69 (Strong), mode of inheritance: AD
• Waardenburg syndrome, IIa 2F (Limited), mode of inheritance: Unknown
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 69; Waardenburg syndrome, type 2F	AD/AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Dermatologic; Ophthalmologic	18083106; 17952075; 19375057; 26522471; 28504826; 35543077

ClinVar

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

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KITLG 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			2	10	1	13
missense	1	1	22	1	2	27
nonsense			1			1
start loss			1			1
frameshift			4			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1	3			4
splice region			2	2	1	5
non coding				15	13	28
Total	1	2	34	26	16

Variants in KITLG

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

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

Position	Type	Phenotype	Significance	ClinVar
12-88505210-ACT-A			Uncertain significance (Dec 18, 2023)
12-88505219-CTT-C			Uncertain significance (Sep 21, 2023)
12-88505250-G-T			Likely benign (Jul 06, 2022)
12-88505250-G-GA			Benign (Oct 03, 2023)
12-88505276-A-T			Likely benign (Jul 21, 2020)
12-88506340-T-C		Inborn genetic diseases	Uncertain significance (Oct 16, 2024)
12-88506370-C-T			Likely benign (Jul 27, 2017)
12-88506380-T-C		Autosomal dominant nonsyndromic hearing loss 69	Conflicting classifications of pathogenicity (Nov 13, 2024)
12-88506469-G-T			Benign (Jun 29, 2018)
12-88507004-A-T			Likely benign (Dec 22, 2020)
12-88507034-G-A		not specified	Likely benign (Jan 15, 2024)
12-88507036-A-G			Uncertain significance (Jun 02, 2022)
12-88507043-T-C			Likely benign (Jul 18, 2023)
12-88507062-A-G			Uncertain significance (May 21, 2021)
12-88507095-G-T			Uncertain significance (Apr 21, 2024)
12-88507103-T-A			Likely benign (Aug 27, 2023)
12-88507103-T-C		KITLG-related disorder	Likely benign (Mar 20, 2019)
12-88507110-G-A			Uncertain significance (Aug 30, 2022)
12-88507113-T-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
12-88507114-C-A		not specified	Benign (Jan 29, 2024)
12-88515401-A-C			Likely benign (Dec 22, 2018)
12-88515550-G-C			Uncertain significance (Aug 28, 2021)
12-88515565-G-A			Likely benign (Jul 29, 2022)
12-88515572-G-T			Uncertain significance (Feb 05, 2024)
12-88515586-CAT-C		Waardenburg syndrome, IIa 2F	Pathogenic (Jul 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KITLG	protein_coding	protein_coding	ENST00000228280	9	88059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.850	0.150	125661	0	4	125665	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.811	114	141	0.808	0.00000658	1826
Missense in Polyphen		43	62.916	0.68345		871
Synonymous	0.106	47	47.9	0.980	0.00000231	482
Loss of Function	3.11	2	15.0	0.133	6.31e-7	197

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000179	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5- trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.
• Disease: DISEASE: Hyperpigmentation with or without hypopigmentation, familial progressive (FPHH) [MIM:145250]: A disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age. Hyperpigmentation has variable intensity, and sometimes is associated with cafe-au-lait macules and larger hypopigmented ash-leaf macules. {ECO:0000269|PubMed:19375057}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, congenital, unilateral or asymmetric (DCUA) [MIM:616697]: An autosomal dominant form of non-syndromic, sensorineural deafness characterized by inability to hear affecting one ear. Some patients suffers from asymmetric, bilateral hearing loss. {ECO:0000269|PubMed:26522471}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Cell Cycle;Differentiation Pathway;Hematopoietic Stem Cell Differentiation;Kit receptor signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Disease;Signal Transduction;melanocyte development and pigmentation pathway;regulation of bad phosphorylation;cdk regulation of dna replication;JAK STAT MolecularVariation 1;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;KitReceptor;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Regulation of KIT signaling;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;JAK STAT pathway and regulation;C-MYB transcription factor network;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Signaling by SCF-KIT;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;GPCR signaling-G alpha i;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Diseases of signal transduction;Signaling events mediated by Stem cell factor receptor (c-Kit) (Consensus)

Recessive Scores

• pRec: 0.801

Intolerance Scores

• loftool: 0.564
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.267
• hipred: Y
• hipred_score: 0.693
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.767

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kitl
• Phenotype: liver/biliary system phenotype; embryo phenotype; pigmentation phenotype; neoplasm; 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); reproductive system phenotype; vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); skeleton phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region 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); craniofacial phenotype

Zebrafish Information Network

• Gene name: kitlga
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: MAPK cascade;ovarian follicle development;neural crest cell migration;positive regulation of leukocyte migration;positive regulation of myeloid leukocyte differentiation;cell adhesion;signal transduction;cell population proliferation;positive regulation of cell population proliferation;male gonad development;regulation of signaling receptor activity;negative regulation of mast cell apoptotic process;embryonic hemopoiesis;ectopic germ cell programmed cell death;positive regulation of MAP kinase activity;positive regulation of melanocyte differentiation;positive regulation of Ras protein signal transduction;phosphatidylinositol phosphorylation;positive regulation of peptidyl-tyrosine phosphorylation;positive regulation of protein kinase B signaling;positive regulation of mast cell proliferation;extrinsic apoptotic signaling pathway in absence of ligand;positive regulation of hematopoietic stem cell proliferation
• Cellular component: extracellular region;extracellular space;cytoplasm;cytoskeleton;plasma membrane;integral component of membrane;lamellipodium;filopodium
• Molecular function: Ras guanyl-nucleotide exchange factor activity;cytokine activity;stem cell factor receptor binding;protein binding;growth factor activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity