KHDC3L

protein-coding

KH domain containing 3 like, subcortical maternal complex member, the group of Subcortical maternal complex

Gene summary

The protein encoded by this gene belongs to the KHDC1 family, members of which contain an atypical KH domain that may not bind RNA like canonical KH domains. This gene is specifically expressed in the oocytes, and recent studies suggest that it may function as a regulator of genomic imprinting in the oocyte. Mutations in this gene are associated with recurrent biparental complete hydatidiform mole. [provided by RefSeq, Dec 2011]

Previous symbols:

C6orf221

MANE transcript

NM_001017361.3

Inheritance

ClinVar variants

P:5U:36B:5

Top phenotype

Hydatidiform mole, recurrent, 2

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr6:73,362,658-73,364,171

External References & Databases

Ensembl (ENSG00000203908)

Transcript & Mutation Effects

hg38 • Region Span ~1.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hydatidiform mole, recurrent, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013671

Submitter: PanelApp Australia

hydatidiform mole, recurrent, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013671

Submitter: Labcorp Genetics (formerly Invitae)

complete hydatidiform moleSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016785

Submitter: Orphanet

Clinical Genomic Database (CGD)

Hydatidiform mole, recurrent, 2AR

Manifestation: Obstetric; Oncologic

Intervention: Obstetric; Oncologic

Rationale: Women are likely to have pregnancies with hydatidiform moles, with a high risk of persistent trophoblastic disease, including requiring chemotherapeutic treatment, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment

Refs: 11932746; 19246479; 21623199; 21885028

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KHDC3L variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 39

Hydatidiform mole, recurrent, 2Total: 8

not providedTotal: 2

KHDC3L-related conditionTotal: 1

not specifiedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001017361.3. 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				1 clinvar		1
missense			35 clinvar	4 clinvar		39
nonsense		1 clinvar				1
start loss	1 clinvar		1 clinvar			2
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	3	2	36	5	0	46

Highest pathogenic variant AF is 0.000035315108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001017361.3	RefSeq	NP_001017361.1	3	MANE Select
ENST00000370367.4	Ensembl	ENSP00000359392.3	3	MANE Select
ENST00001140189.1	Ensembl	ENSP00000809709.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process

Molecular Function

RNA binding
protein binding

Cellular Component

protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370367
Coding exons: 3
Length: 1495
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125743
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.196	139	146	0.954	0.0000114	1389
Missense (PolyPhen)		34	38.795	0.87639		391
Synonymous	1.06	51	61.6	0.827	0.00000473	456
Loss of Function	1.36	2	5.41	0.370	3.02e-7	51

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Hydatidiform mole, recurrent, 2 (HYDM2) [MIM:614293]: A disorder characterized by excessive trophoblast development that produces a growing mass of tissue inside the uterus at the beginning of a pregnancy. It leads to abnormal pregnancies with no embryo, and cystic degeneration of the chorionic villi. {ECO:0000269|PubMed:21885028}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0846

Intolerance Scores

RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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