KHDC4

Summary

KHDC4 (KH domain containing 4, pre-mRNA splicing factor, HGNC:29145) is a protein-coding gene on chromosome 1q22, encoding KH homology domain-containing protein 4 (Q7Z7F0). RNA-binding protein involved in pre-mRNA splicing.

Enables RNA binding activity. Involved in mRNA splice site recognition. Located in cytoplasm; nucleoplasm; and spliceosomal complex.

Source: NCBI Gene 22889 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_014949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29145
Approved symbol	KHDC4
Name	KH domain containing 4, pre-mRNA splicing factor
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	BLOM7, SNORA80EHG
Ensembl gene	ENSG00000132680
Ensembl biotype	protein_coding
OMIM	619370
Entrez	22889

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding_CDS_not_defined, 5 protein_coding

ENST00000368319, ENST00000368320, ENST00000368321, ENST00000465953, ENST00000466520, ENST00000466713, ENST00000478002, ENST00000482337, ENST00000483237, ENST00000491599, ENST00000916409, ENST00000916410

RefSeq mRNA: 1 — MANE Select: NM_014949 NM_014949

CCDS: CCDS30885

Canonical transcript exons

ENST00000368321 — 14 exons

Exon	Start	End
ENSE00001054158	155916625	155916737
ENSE00001446866	155913045	155914320
ENSE00001446867	155934336	155934413
ENSE00003464365	155923627	155923687
ENSE00003478287	155915873	155915964
ENSE00003572139	155929296	155929375
ENSE00003581371	155921375	155921628
ENSE00003597421	155926676	155926839
ENSE00003599469	155921861	155921918
ENSE00003609530	155927104	155927156
ENSE00003622417	155933633	155933849
ENSE00003626984	155917499	155917672
ENSE00003639961	155925632	155925843
ENSE00003660321	155929712	155929840

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.1341 / max 226.2115, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15001	16.4369	1800
15000	7.5798	1734
14997	0.1174	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	96.84	gold quality
endocervix	UBERON:0000458	96.10	gold quality
pylorus	UBERON:0001166	96.09	gold quality
corpus epididymis	UBERON:0004359	95.95	gold quality
right ovary	UBERON:0002118	95.86	gold quality
cardia of stomach	UBERON:0001162	95.82	gold quality
tendon of biceps brachii	UBERON:0008188	95.81	gold quality
left ovary	UBERON:0002119	95.76	gold quality
skin of hip	UBERON:0001554	95.55	gold quality
ectocervix	UBERON:0012249	95.41	gold quality
rectum	UBERON:0001052	95.40	gold quality
minor salivary gland	UBERON:0001830	95.32	gold quality
adenohypophysis	UBERON:0002196	95.26	gold quality
ovary	UBERON:0000992	95.12	gold quality
pituitary gland	UBERON:0000007	95.11	gold quality
fundus of stomach	UBERON:0001160	95.09	gold quality
tibial nerve	UBERON:0001323	95.05	gold quality
upper leg skin	UBERON:0004262	95.04	gold quality
metanephros cortex	UBERON:0010533	94.99	gold quality
vagina	UBERON:0000996	94.95	gold quality
body of uterus	UBERON:0009853	94.91	gold quality
cerebellar hemisphere	UBERON:0002245	94.80	gold quality
cerebellar cortex	UBERON:0002129	94.75	gold quality
body of stomach	UBERON:0001161	94.71	gold quality
renal medulla	UBERON:0000362	94.67	gold quality
right uterine tube	UBERON:0001302	94.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.62	gold quality
mouth mucosa	UBERON:0003729	94.56	gold quality
seminal vesicle	UBERON:0000998	94.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.27
E-MTAB-7606	no	17.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting KHDC4, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-579-3P	99.86	71.66	3628

Literature-anchored findings (GeneRIF, showing 2)

• Blom7alpha is a novel heterogeneous nuclear ribonucleoprotein K homology domain protein involved in pre-mRNA splicing and interacting with the CDC5L-SNEV(Prp19-Pso4) complex. (PMID:19641227)
• Results suggest that the RNA binding activity of Blom7alpha might be required for pre-mRNA splicing catalysis. (PMID:23144703)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	khdc4	ENSDARG00000035023
mus_musculus	Khdc4	ENSMUSG00000028060
rattus_norvegicus	Khdc4	ENSRNOG00000020139

Protein

Protein identifiers

KH homology domain-containing protein 4 — Q7Z7F0 (reviewed: Q7Z7F0)

Alternative names: Brings lots of money 7, Pre-mRNA splicing factor protein KHDC4

All UniProt accessions (1): Q7Z7F0

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein involved in pre-mRNA splicing. Interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. Involved in regulating splice site selection. Binds preferentially RNA with A/C rich sequences and poly-C stretches.

Subunit / interactions. Interacts with PRPF19. Interacts with U2AF65.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitous. Expressed at high level in skeletal muscle, kidney, heart, brain and liver.

Domain organisation. The C-terminal part is necessary for the interaction with the PRP19C/Prp19 complex/NTC/Nineteen complex. The KH domains mediate RNA-binding.

Miscellaneous. Interacts with U2AF65.

Similarity. Belongs to the KHDC4 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q7Z7F0-1	1, Alpha, Blom7alpha	yes
Q7Z7F0-2	2, Beta, KIAA0907
Q7Z7F0-3	3, Gamma
Q7Z7F0-4	4

RefSeq proteins (1): NP_055764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031121	RIK/BLOM7	Family
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR047889	KHDC4_KH-I_second	Domain
IPR047890	KHDC4_KH-I_first	Domain
IPR055256	KH_1_KHDC4/BBP-like	Domain
IPR056149	PRP5/DDX46/KHDC4_KH	Domain

Pfam: PF22675, PF23469

UniProt features (31 total): compositionally biased region 6, splice variant 6, strand 4, helix 4, region of interest 4, domain 2, modified residue 2, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YQR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7F0-F1	63.07	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 571, 572

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): GCM_GSPT1, KAAB_FAILED_HEART_ATRIUM_DN, BROWNE_HCMV_INFECTION_8HR_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, chr1q22, GOBP_MRNA_SPLICE_SITE_RECOGNITION, CAIRO_HEPATOBLASTOMA_UP, CTTTGTA_MIR524, ACEVEDO_LIVER_CANCER_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, TTTGCAC_MIR19A_MIR19B, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN

GO Biological Process (3): mRNA splice site recognition (GO:0006376), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), spliceosomal complex (GO:0005681)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
cellular anatomical structure	2
spliceosomal complex assembly	1
protein-RNA complex assembly	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

470 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KHDC4	PRPF19	Q9UMS4	571
KHDC4	LUC7L	Q9NQ29	475
KHDC4	FUBP3	Q96I24	473
KHDC4	YAE1	Q9NRH1	471
KHDC4	EFCAB12	Q6NXP0	462
KHDC4	CDC5L	Q99459	462
KHDC4	SF1	Q15637	456
KHDC4	ZNF529	Q6P280	450
KHDC4	LUC7L3	O95232	445
KHDC4	CWC15	Q9P013	440
KHDC4	SMC5	Q8IY18	429
KHDC4	NOVA1	P51513	404
KHDC4	CHERP	Q8IWX8	387
KHDC4	SLC68A1	Q14CX5	384
KHDC4	RABL6	Q3YEC7	379

IntAct

29 interactions, top by confidence:

A	B	Type	Score
CLOCK	BMAL1	psi-mi:“MI:0914”(association)	0.880
KHDC4	RBM39	psi-mi:“MI:0915”(physical association)	0.560
RBM39	KHDC4	psi-mi:“MI:0915”(physical association)	0.560
PUF60	KHDC4	psi-mi:“MI:0915”(physical association)	0.560
KHDC4	TYMP	psi-mi:“MI:0914”(association)	0.530
STARD7	TLE5	psi-mi:“MI:0914”(association)	0.530
U2AF2	KHDC4	psi-mi:“MI:0915”(physical association)	0.520
ZDHHC17	KHDC4	psi-mi:“MI:0915”(physical association)	0.370
KHDC4	IGKC	psi-mi:“MI:0914”(association)	0.350
STARD7	TLE3	psi-mi:“MI:0914”(association)	0.350
lpqN	SOWAHD	psi-mi:“MI:0914”(association)	0.350
KHDC4	DNAJC5	psi-mi:“MI:2364”(proximity)	0.270
NOLC1	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270
U2AF2	NACA	psi-mi:“MI:2364”(proximity)	0.270
KHDC4	SF1	psi-mi:“MI:0915”(physical association)	0.000
SF1	KHDC4	psi-mi:“MI:0915”(physical association)	0.000
KHDC4		psi-mi:“MI:0915”(physical association)	0.000
KHDC4	maP3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (77): KIAA0907 (Two-hybrid), KIAA0907 (Two-hybrid), KIAA0907 (Affinity Capture-RNA), KIAA0907 (Affinity Capture-RNA), KIAA0907 (Affinity Capture-RNA), KIAA0907 (Two-hybrid), KIAA0907 (Affinity Capture-MS), KIAA0907 (Two-hybrid), KIAA0907 (Co-fractionation), KIAA0907 (Co-fractionation), KIAA0907 (Proximity Label-MS), KIAA0907 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), CALML5 (Affinity Capture-MS), IGHG2 (Affinity Capture-MS)

ESM2 similar proteins: A0JM64, A4IHD9, B5DF93, D3ZTQ1, E7F1H9, O70305, P70501, Q12872, Q13625, Q2NLB0, Q2T9I5, Q32SG5, Q3TC46, Q3TCX3, Q3USH5, Q498K9, Q566L7, Q5R413, Q5R8Q4, Q5SFM8, Q5T8P6, Q5ZL54, Q62415, Q66IJ0, Q68FI1, Q6DDU9, Q6GP15, Q6NXI6, Q6NZ18, Q6NZN0, Q6PEH8, Q7Z7F0, Q86TB9, Q8BG81, Q8CG79, Q8CGC4, Q8IZD4, Q8K2F8, Q8ND56, Q8R205

Diamond homologs: A0JM64, Q2NLB0, Q3TCX3, Q5ZL54, Q6NZ18, Q7Z7F0, Q8H0U8, Q9LIA4, Q9SF41, A7ENE0, Q32SG5, Q4TVV3, Q553B1, Q2HAD8, Q75GR5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Splicing - Major Pathway	5	19.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1507 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155914321:C:CC	acceptor_gain	1.0000
1:155915867:ACTC:A	donor_loss	1.0000
1:155915868:CTCA:C	donor_loss	1.0000
1:155915869:TCA:T	donor_loss	1.0000
1:155915870:CACC:C	donor_loss	1.0000
1:155915871:A:AT	donor_loss	1.0000
1:155915880:C:CA	donor_gain	1.0000
1:155915961:CTGC:C	acceptor_gain	1.0000
1:155915962:TGC:T	acceptor_gain	1.0000
1:155915963:GC:G	acceptor_gain	1.0000
1:155915964:CCTAT:C	acceptor_gain	1.0000
1:155915965:C:CC	acceptor_gain	1.0000
1:155915968:T:C	acceptor_gain	1.0000
1:155915968:T:TC	acceptor_gain	1.0000
1:155916620:CTTA:C	donor_loss	1.0000
1:155916621:TTACC:T	donor_loss	1.0000
1:155916622:TA:T	donor_loss	1.0000
1:155916623:ACCT:A	donor_loss	1.0000
1:155916624:C:CG	donor_loss	1.0000
1:155916624:CCTGT:C	donor_gain	1.0000
1:155916734:CATG:C	acceptor_gain	1.0000
1:155916738:C:CC	acceptor_gain	1.0000
1:155917493:TTTAA:T	donor_loss	1.0000
1:155917494:TTAAC:T	donor_loss	1.0000
1:155917496:AACCT:A	donor_loss	1.0000
1:155917497:A:AT	donor_loss	1.0000
1:155917497:A:C	donor_gain	1.0000
1:155917498:CCTG:C	donor_loss	1.0000
1:155917671:CT:C	acceptor_gain	1.0000
1:155917673:C:CC	acceptor_gain	1.0000

AlphaMissense

3950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155921917:A:T	V319D	1.000
1:155923637:A:G	L315P	1.000
1:155923637:A:T	L315H	1.000
1:155923645:A:C	C312W	1.000
1:155923646:C:T	C312Y	1.000
1:155923647:A:G	C312R	1.000
1:155923649:A:G	L311P	1.000
1:155923658:G:T	A308D	1.000
1:155923659:C:G	A308P	1.000
1:155923667:A:G	L305P	1.000
1:155923685:T:C	H299R	1.000
1:155925635:A:T	I297N	1.000
1:155925641:A:T	I295N	1.000
1:155925654:C:T	E291K	1.000
1:155925655:A:C	F290L	1.000
1:155925655:A:T	F290L	1.000
1:155925657:A:G	F290L	1.000
1:155925665:C:G	R287P	1.000
1:155925681:C:T	E282K	1.000
1:155925701:C:A	G275V	1.000
1:155925701:C:G	G275A	1.000
1:155925701:C:T	G275D	1.000
1:155925702:C:A	G275C	1.000
1:155925702:C:G	G275R	1.000
1:155925702:C:T	G275S	1.000
1:155925704:C:G	R274P	1.000
1:155925707:A:G	L273P	1.000
1:155925707:A:T	L273Q	1.000
1:155925713:A:T	V271D	1.000
1:155925719:G:T	A269D	1.000

dbSNP variants (sampled 300 via entrez): RS1000006697 (1:155932886 G>A,C), RS1000124773 (1:155935243 GAC>G), RS1000323098 (1:155928816 G>A), RS1000938679 (1:155919923 C>T), RS1001187392 (1:155933214 T>C), RS1001258993 (1:155927807 A>C,G), RS1001347448 (1:155914560 A>G), RS1001406985 (1:155920244 C>G), RS1001697220 (1:155926295 T>C), RS1002126153 (1:155931626 T>C), RS1002278779 (1:155912743 C>A,G,T), RS1002298863 (1:155912637 AGAACCACTT>A), RS1002531475 (1:155919211 A>C), RS1002788468 (1:155923235 T>C), RS1002810304 (1:155934362 C>A,T)

Disease associations

OMIM: gene MIM:619370 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
nickel chloride	decreases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
resorcinol	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ozone	increases abundance, affects cotreatment, increases oxidation	1
Quercetin	increases expression	1
Dronabinol	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1V6	Abcam HeLa KHDC4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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