KHDC1

Summary

KHDC1 (KH domain containing 1, HGNC:21366) is a protein-coding gene on chromosome 6q13, encoding KH homology domain-containing protein 1 (Q4VXA5).

Predicted to enable identical protein binding activity and poly(U) RNA binding activity. Predicted to be located in membrane. Predicted to be active in cytoplasm.

Source: NCBI Gene 80759 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_030568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21366
Approved symbol	KHDC1
Name	KH domain containing 1
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	MGC10818, bA257K9.4, NDG1, Em:AC019205.8
Ensembl gene	ENSG00000135314
Ensembl biotype	protein_coding
OMIM	611688
Entrez	80759

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000257765, ENST00000370384, ENST00000433730, ENST00000474593, ENST00000484801, ENST00000881427, ENST00000881429, ENST00000881430, ENST00000881431, ENST00000925611, ENST00000925612, ENST00000925613, ENST00000925614, ENST00000925615, ENST00000925616, ENST00000925617, ENST00000961955, ENST00000961956, ENST00000961957, ENST00000961958

RefSeq mRNA: 4 — MANE Select: NM_030568 NM_001251874, NM_001395215, NM_001395216, NM_030568

CCDS: CCDS43480, CCDS59027

Canonical transcript exons

ENST00000257765 — 4 exons

Exon	Start	End
ENSE00001594408	73241314	73241728
ENSE00003550479	73242406	73242530
ENSE00003788858	73242055	73242237
ENSE00003978118	73262774	73263196

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 83.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.7708 / max 42.3558, expressed in 1336 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74352	2.4603	1030
74351	1.3105	733

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.92	gold quality
prefrontal cortex	UBERON:0000451	83.81	gold quality
right frontal lobe	UBERON:0002810	83.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.05	gold quality
anterior cingulate cortex	UBERON:0009835	82.69	gold quality
cerebellar hemisphere	UBERON:0002245	82.61	gold quality
cerebellar cortex	UBERON:0002129	82.41	gold quality
nucleus accumbens	UBERON:0001882	81.34	gold quality
caudate nucleus	UBERON:0001873	81.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.18	gold quality
cerebellum	UBERON:0002037	80.74	gold quality
neocortex	UBERON:0001950	80.45	gold quality
frontal cortex	UBERON:0001870	80.44	gold quality
ventricular zone	UBERON:0003053	80.28	gold quality
putamen	UBERON:0001874	80.23	gold quality
adenohypophysis	UBERON:0002196	79.43	gold quality
embryo	UBERON:0000922	78.80	gold quality
ganglionic eminence	UBERON:0004023	78.80	gold quality
pituitary gland	UBERON:0000007	78.76	gold quality
amygdala	UBERON:0001876	78.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.35	gold quality
cerebral cortex	UBERON:0000956	78.25	gold quality
hypothalamus	UBERON:0001898	78.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.11	gold quality
forebrain	UBERON:0001890	77.68	gold quality
brain	UBERON:0000955	77.34	gold quality
stromal cell of endometrium	CL:0002255	76.39	gold quality
cortical plate	UBERON:0005343	76.27	gold quality
spinal cord	UBERON:0002240	74.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	3.96
E-ANND-3	no	2.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting KHDC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-6729-3P	96.91	66.79	703

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Khdc1c	ENSMUSG00000041722
mus_musculus	Khdc1a	ENSMUSG00000067750
mus_musculus	Khdc1b	ENSMUSG00000085079
rattus_norvegicus	Khdc1	ENSRNOG00000028595
rattus_norvegicus	LOC134483627	ENSRNOG00000063212
rattus_norvegicus		ENSRNOG00000069823

Paralogs (2): DPPA5 (ENSG00000203909), KHDC1L (ENSG00000256980)

Protein

Protein identifiers

KH homology domain-containing protein 1 — Q4VXA5 (reviewed: Q4VXA5)

All UniProt accessions (2): A6PVU5, Q4VXA5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the KHDC1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q4VXA5-1	1	yes
Q4VXA5-2	2

RefSeq proteins (4): NP_001238803, NP_001382144, NP_001382145, NP_085045* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031952	MOEP19_KH-like	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF16005

UniProt features (6 total): transmembrane region 2, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4VXA5-F1	69.79	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): MODULE_205, MODULE_207, TGFB_UP.V1_UP, STK33_DN, STK33_SKM_DN, KRAS.PROSTATE_UP.V1_UP, ZNF30_TARGET_GENES, ZNF329_TARGET_GENES, ZNF423_TARGET_GENES, ZNF610_TARGET_GENES, MIR4262, MIR6830_3P, MIR21_5P, MIR1229_3P, MIR6511A_3P_MIR6511B_3P

GO Biological Process (0):

GO Molecular Function (1): RNA binding (GO:0003723)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nucleic acid binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KHDC1	KHDC3L	Q587J8	981
KHDC1	DPPA5	A6NC42	980
KHDC1	OOEP	A6NGQ2	974
KHDC1	TRIM43	Q96BQ3	697
KHDC1	LEUTX	A8MZ59	627
KHDC1	PRAMEF2	O60811	623
KHDC1	PRAMEF1	O95521	621
KHDC1	MBD3L2	Q8NHZ7	603
KHDC1	ZSCAN4	Q8NAM6	578
KHDC1	DUX4L2	P0CJ85	570
KHDC1	RFPL4B	Q6ZWI9	479
KHDC1	RFPL2	O75678	476
KHDC1	ZNF799	Q96GE5	476
KHDC1	PRAMEF11	O60813	475
KHDC1	RFPL1	O75677	447

IntAct

3 interactions, top by confidence:

A	B	Type	Score
	FAM171A2	psi-mi:“MI:0914”(association)	0.350
KHDC1	AIP	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): KHDC1 (Two-hybrid), KHDC1 (Two-hybrid), KHDC1 (Two-hybrid), LONRF1 (Two-hybrid), PROP1 (Two-hybrid), KHDC1 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), AIP (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS), RAD51 (Affinity Capture-MS), TTC28 (Affinity Capture-MS), DDB2 (Affinity Capture-MS), DNAJB5 (Affinity Capture-MS), ERF (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8VHF7, A0JM23, A2QRA0, A4IIA7, A4IIV4, A6NFN9, A6NHR9, A7MBF6, F4IG73, F4JSE7, O17482, O95876, P12540, P21784, P34089, P38899, P55895, P56696, Q08AW4, Q0D2D7, Q12789, Q13829, Q28DC9, Q2WGJ8, Q3E7Y5, Q3UUE9, Q4R907, Q4VXA5, Q5BK83, Q5EA90, Q5F476, Q5HZS2, Q5M9F0, Q5RAX4, Q5RBH4, Q5RD21, Q6AYL6, Q6DGA7, Q6PIY5, Q70XZ2

Diamond homologs: P0C7A0, Q3UWR2, Q4KL78, Q4VXA5, Q5JSQ8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

38 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1073 predictions. Top by Δscore:

Variant	Effect	Δscore
6:73241620:A:AC	donor_gain	1.0000
6:73241620:AT:A	donor_gain	1.0000
6:73241620:ATC:A	donor_gain	1.0000
6:73242234:TGCC:T	acceptor_gain	1.0000
6:73242401:CTCA:C	donor_loss	1.0000
6:73242402:TCA:T	donor_loss	1.0000
6:73242403:CACCG:C	donor_loss	1.0000
6:73242404:A:AC	donor_gain	1.0000
6:73242404:A:T	donor_loss	1.0000
6:73242405:C:CA	donor_gain	1.0000
6:73242405:CCG:C	donor_gain	1.0000
6:73263030:C:CA	donor_gain	1.0000
6:73241621:T:C	donor_gain	0.9900
6:73241621:T:TA	donor_gain	0.9900
6:73241724:CAGGC:C	acceptor_gain	0.9900
6:73241725:AGGCC:A	acceptor_loss	0.9900
6:73241726:GGC:G	acceptor_gain	0.9900
6:73241727:GC:G	acceptor_gain	0.9900
6:73241727:GCCTG:G	acceptor_loss	0.9900
6:73241728:CC:C	acceptor_gain	0.9900
6:73241728:CCT:C	acceptor_loss	0.9900
6:73241729:C:CC	acceptor_gain	0.9900
6:73241729:CTG:C	acceptor_loss	0.9900
6:73241730:T:G	acceptor_loss	0.9900
6:73242237:CCT:C	acceptor_loss	0.9900
6:73242238:C:A	acceptor_loss	0.9900
6:73242239:T:C	acceptor_loss	0.9900
6:73242404:A:C	donor_loss	0.9900
6:73242404:AC:A	donor_gain	0.9900
6:73242405:C:CC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015999 (6:73258313 C>T), RS1000080575 (6:73289678 A>AT), RS1000102538 (6:73247904 C>CCCTT), RS1000105285 (6:73254636 T>C), RS1000315180 (6:73262204 A>T), RS1000345363 (6:73301860 G>A), RS1000365771 (6:73260879 T>C), RS1000384044 (6:73282487 C>A,T), RS1000392616 (6:73268042 T>C), RS1000408173 (6:73272632 C>G,T), RS1000559177 (6:73247622 G>A), RS1000569282 (6:73307703 C>G), RS1000580309 (6:73308049 C>T), RS1000641864 (6:73300963 T>A), RS1000658942 (6:73296029 C>T)

Disease associations

OMIM: gene MIM:611688 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_472	Metabolite levels	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
Valproic Acid	increases expression, affects expression	2
aristolochic acid I	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
ICG 001	increases expression	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	increases methylation	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.