KDM1A

lysine demethylase 1A, the group of MicroRNA protein coding host genes|Lysine demethylases

Basic information

Region (hg38): 1:23019442-23083689

Previous symbols: [ "AOF2", "KDM1" ]

Links

ENSG00000004487 ∙ NCBI:23028 ∙ OMIM:609132 ∙ HGNC:29079 ∙ Uniprot:O60341 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome (Moderate), mode of inheritance: AD
• palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome (Strong), mode of inheritance: AD
• palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cleft palate, psychomotor retardation, and distinctive facial features	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	24838796; 26656649

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM1A gene.

• not provided (193 variants)
• Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome (18 variants)
• Inborn genetic diseases (15 variants)
• not specified (9 variants)
• KDM1A-related condition (4 variants)
• Intellectual disability (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)
• Neurodevelopmental and congenital anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM1A 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	47	9	57
missense	3	5	86	1		95
nonsense		1	5			6
start loss						0
frameshift			7			7
inframe indel			1	1	1	3
splice donor/acceptor (+/-2bp)						0
splice region			6	8		14
non coding				24	20	44
Total	3	6	100	73	30

Variants in KDM1A

This is a list of pathogenic ClinVar variants found in the KDM1A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-23019601-T-C			Uncertain significance (Mar 23, 2023)
1-23019614-GGCGGCAGCCGCGGCGGCGGCGGCTGCA-G			Benign (Jan 22, 2024)
1-23019617-G-A			Likely benign (May 15, 2023)
1-23019623-C-CGCG			Conflicting classifications of pathogenicity (Mar 30, 2023)
1-23019627-G-T			Uncertain significance (Dec 26, 2022)
1-23019631-C-T			Uncertain significance (Jan 10, 2024)
1-23019635-G-A			Likely benign (Jan 12, 2024)
1-23019648-G-A			Uncertain significance (Mar 01, 2023)
1-23019656-G-A			Likely benign (Oct 13, 2023)
1-23019659-G-A			Likely benign (Jul 11, 2022)
1-23019668-C-T			Likely benign (Jun 19, 2022)
1-23019673-G-C			Uncertain significance (Sep 27, 2022)
1-23019688-C-G			Uncertain significance (Feb 03, 2023)
1-23019719-C-A			Likely benign (Dec 07, 2023)
1-23019722-G-A			Likely benign (Oct 13, 2022)
1-23019724-G-A			Uncertain significance (Dec 09, 2019)
1-23019727-T-C		Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome	Uncertain significance (Apr 24, 2020)
1-23019732-G-A		Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome • not specified • KDM1A-related disorder	Conflicting classifications of pathogenicity (Feb 01, 2024)
1-23019740-C-G			Likely benign (Nov 28, 2023)
1-23019740-C-T			Likely benign (Sep 01, 2023)
1-23019744-G-A			Uncertain significance (Nov 01, 2023)
1-23019750-C-T		KDM1A-related disorder	Likely benign (Dec 30, 2023)
1-23019756-G-A		Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome	Uncertain significance (Aug 28, 2019)
1-23019757-C-T			Uncertain significance (Jan 31, 2023)
1-23019777-C-A		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM1A	protein_coding	protein_coding	ENST00000400181	21	64242

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00333	125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.68	174	455	0.383	0.0000242	5628
Missense in Polyphen		37	171.37	0.21591		1929
Synonymous	1.57	141	167	0.845	0.00000914	1751
Loss of Function	5.46	7	47.7	0.147	0.00000263	563

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000881	0.0000881
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000802	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.0000332	0.0000327
Other	0.000336	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr- 6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E- cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7. {ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:15620353, ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20562920}.
• Disease: DISEASE: Cleft palate, psychomotor retardation, and distinctive facial features (CPRF) [MIM:616728]: A syndrome characterized by cleft palate, developmental delay, psychomotor retardation, and facial dysmorphic features including a prominent forehead, slightly arched eyebrows, elongated palpebral fissures, a wide nasal bridge, thin lips, and widely spaced teeth. Cleft palate is a congenital fissure of the soft and/or hard palate, due to faulty fusion. {ECO:0000269|PubMed:23020937, ECO:0000269|PubMed:24838796, ECO:0000269|PubMed:26656649}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Androgen receptor signaling pathway;Signal Transduction;Factors involved in megakaryocyte development and platelet production;HDACs deacetylate histones;HDMs demethylate histones;Chromatin modifying enzymes;Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;RHO GTPases activate PKNs;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PTEN gene transcription;Hemostasis;Coregulation of Androgen receptor activity;PTEN Regulation;PIP3 activates AKT signaling;Signaling by Nuclear Receptors;Chromatin organization;Notch signaling pathway;Estrogen-dependent gene expression;ESR-mediated signaling;Intracellular signaling by second messengers;Notch-mediated HES/HEY network (Consensus)

Recessive Scores

• pRec: 0.211

Intolerance Scores

• loftool: 0.337
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.418
• hipred: Y
• hipred_score: 0.746
• ghis: 0.667

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kdm1a
• 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; renal/urinary system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; 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); homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: kdm1a
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;alternative mRNA splicing, via spliceosome;positive regulation of neuroblast proliferation;regulation of transcription by RNA polymerase II;protein demethylation;blood coagulation;regulation of double-strand break repair via homologous recombination;positive regulation of neuron projection development;histone deacetylation;cerebral cortex development;negative regulation of protein binding;histone H3-K9 demethylation;positive regulation of histone ubiquitination;cellular response to UV;histone H3-K4 demethylation;positive regulation of chromatin binding;neuron maturation;negative regulation of DNA binding;negative regulation of DNA-binding transcription factor activity;negative regulation of DNA damage response, signal transduction by p53 class mediator;positive regulation of cell size;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;guanine metabolic process;positive regulation of DNA-binding transcription factor activity;muscle cell development;oxidation-reduction process;response to fungicide;cellular response to cAMP;cellular response to gamma radiation;positive regulation of cold-induced thermogenesis;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;regulation of cellular protein localization
• Cellular component: nuclear chromosome, telomeric region;nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;protein-containing complex;DNA repair complex
• Molecular function: p53 binding;chromatin binding;histone deacetylase activity;protein binding;transcription factor binding;oxidoreductase activity;enzyme binding;nuclear receptor transcription coactivator activity;demethylase activity;histone demethylase activity;histone demethylase activity (H3-K4 specific);histone demethylase activity (H3-K9 specific);histone demethylase activity (H3-dimethyl-K4 specific);telomeric DNA binding;MRF binding;transcription regulatory region DNA binding;flavin adenine dinucleotide binding;androgen receptor binding;telomeric repeat-containing RNA binding