JMJD1C

protein-coding

jumonji domain containing 1C, the group of Lysine demethylases|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Previous symbols:

TRIP8

MANE transcript

NM_032776.3

Inheritance

ClinVar variants

P:3U:980B:439

Top phenotype

intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr10:63,167,221-63,521,850

External References & Databases

Ensembl (ENSG00000171988)

Transcript & Mutation Effects

hg38 • Region Span ~354.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Illumina

intellectual disabilitySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0001071

Submitter: PanelApp Australia

22q11.2 deletion syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018923

Submitter: Orphanet

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to JMJD1C variants in ClinVar

13 Conditions Cataloged

Early Myoclonic EncephalopathyTotal: 1396

not specifiedTotal: 269

not providedTotal: 108

JMJD1C-related disorderTotal: 38

JMJD1C-associated Neurodevelopmental DisorderTotal: 5

Neurodevelopmental disorderTotal: 3

Intellectual disabilityTotal: 2

See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032776.3. 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			3 clinvar	363 clinvar	17 clinvar	383
missense		1 clinvar	953 clinvar	52 clinvar	7 clinvar	1013
nonsense			6 clinvar			6
start loss						0
frameshift	2 clinvar		8 clinvar			10
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	2	1	980	415	24	1422

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032776.3	RefSeq	NP_116165.1	26	MANE Select
ENST00000399262.7	Ensembl	ENSP00000382204.2	26	MANE Select
NM_001282948.2	RefSeq	NP_001269877.1	23	Standard
NM_001318153.2	RefSeq	NP_001305082.1	20	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
jmjd1cb	Danio rerio	Structure: myeloid cell development Quality: absent abnormal

Gene / Model

Organism

Observed Phenotype

jmjd1cb

Danio rerio

Structure: myeloid cell development

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transcriptional misregulation in cancer - Homo sapiens (human)
Pathways Affected in Adenoid Cystic Carcinoma
Factors involved in megakaryocyte development and platelet production
Hemostasis

Biological Process

regulation of transcription, DNA-templated
blood coagulation
histone H3-K9 demethylation
oxidation-reduction process

Molecular Function

transcription regulatory region sequence-specific DNA binding
protein binding
chromatin DNA binding
histone demethylase activity (H3-K9 specific)
metal ion binding

Cellular Component

chromatin
nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399262
Coding exons: 26
Length: 298742
Individuals with no LoFs: 124790
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 124801
p: 0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	1138	1.29e+3	0.881	0.0000630	16782
Missense (PolyPhen)		270	478.95	0.56373		6199
Synonymous	-1.81	495	446	1.11	0.0000214	4741
Loss of Function	9.35	3	108	0.0278	0.00000544	1415

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000090	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000028	0.000026	rare
South Asian	0	0.0	absent
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May be involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.0285
RVIS EVS: -0.55
RVIS percentile EVS: 19.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.836

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High