KLHDC9

Summary

KLHDC9 (kelch domain containing 9, HGNC:28489) is a protein-coding gene on chromosome 1q23.3, encoding Kelch domain-containing protein 9 (Q8NEP7).

Enables cyclin binding activity.

Source: NCBI Gene 126823 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_152366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28489
Approved symbol	KLHDC9
Name	kelch domain containing 9
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	KARCA1
Ensembl gene	ENSG00000162755
Ensembl biotype	protein_coding
OMIM	617375
Entrez	126823

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000368011, ENST00000392191, ENST00000392192, ENST00000469647, ENST00000471613, ENST00000475934, ENST00000490724, ENST00000494418, ENST00000851620, ENST00000917942

RefSeq mRNA: 2 — MANE Select: NM_152366 NM_001007255, NM_152366

CCDS: CCDS30919, CCDS41425

Canonical transcript exons

ENST00000368011 — 4 exons

Exon	Start	End
ENSE00003489499	161099598	161099796
ENSE00003499264	161099346	161099505
ENSE00003576772	161100061	161100346
ENSE00003844125	161098361	161099062

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 97.16.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7622 / max 72.1736, expressed in 705 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6195	1.4612	613
6196	0.3010	156

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	97.16	gold quality
left testis	UBERON:0004533	97.15	gold quality
adult organism	UBERON:0007023	95.48	gold quality
testis	UBERON:0000473	95.21	gold quality
right uterine tube	UBERON:0001302	95.04	gold quality
sperm	CL:0000019	94.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.68	gold quality
bronchial epithelial cell	CL:0002328	93.59	gold quality
right frontal lobe	UBERON:0002810	92.73	gold quality
bronchus	UBERON:0002185	92.66	gold quality
nucleus accumbens	UBERON:0001882	92.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.89	gold quality
caudate nucleus	UBERON:0001873	91.82	gold quality
anterior cingulate cortex	UBERON:0009835	91.76	gold quality
kidney epithelium	UBERON:0004819	91.51	silver quality
putamen	UBERON:0001874	91.28	gold quality
adenohypophysis	UBERON:0002196	91.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.97	gold quality
prefrontal cortex	UBERON:0000451	90.96	gold quality
pituitary gland	UBERON:0000007	90.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.76	gold quality
hypothalamus	UBERON:0001898	90.75	gold quality
cerebellar hemisphere	UBERON:0002245	90.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.16	gold quality
frontal cortex	UBERON:0001870	90.04	gold quality
cerebellar cortex	UBERON:0002129	89.99	gold quality
neocortex	UBERON:0001950	89.65	gold quality
amygdala	UBERON:0001876	89.14	gold quality
cerebellum	UBERON:0002037	88.91	gold quality
forebrain	UBERON:0001890	88.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting KLHDC9, 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-10527-5P	99.91	72.28	3754
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-627-5P	95.51	66.80	509
HSA-MIR-4330	95.44	66.39	993

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hcfc1b	ENSDARG00000012519
danio_rerio	hcfc1a	ENSDARG00000015990
danio_rerio	hcfc2	ENSDARG00000058127
mus_musculus	Klhdc9	ENSMUSG00000045259
rattus_norvegicus	Klhdc9	ENSRNOG00000004022
drosophila_melanogaster	Hcf	FBGN0039904
caenorhabditis_elegans		WBGENE00001827

Paralogs (10): FBXO42 (ENSG00000037637), LZTR1 (ENSG00000099949), KLHDC4 (ENSG00000104731), HCFC2 (ENSG00000111727), KLHDC3 (ENSG00000124702), KLHDC10 (ENSG00000128607), RABEPK (ENSG00000136933), KLHDC2 (ENSG00000165516), HCFC1 (ENSG00000172534), KLHDC1 (ENSG00000197776)

Protein

Protein identifiers

Kelch domain-containing protein 9 — Q8NEP7 (reviewed: Q8NEP7)

Alternative names: Kelch/ankyrin repeat-containing cyclin A1-interacting protein

All UniProt accessions (1): Q8NEP7

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with CCNA1.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NEP7-1	1	yes
Q8NEP7-2	2
Q8NEP7-3	3

RefSeq proteins (2): NP_001007256, NP_689579* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011043	Gal_Oxase/kelch_b-propeller	Homologous_superfamily
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR042941	KLDC9	Family

Pfam: PF24681

UniProt features (12 total): splice variant 4, repeat 3, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEP7-F1	93.42	0.87

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): RACCACAR_AML_Q6, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, AML1_01, ACEVEDO_LIVER_CANCER_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, OSF2_Q6, CAGCTTT_MIR320, GOMF_CYCLIN_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEN_LIVER_METABOLISM_QTL_CIS, WHITFIELD_CELL_CYCLE_G2_M, MARTENS_TRETINOIN_RESPONSE_DN, LU_EZH2_TARGETS_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, ASH1L_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): cyclin binding (GO:0030332), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1

Protein interactions and networks

STRING

750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHDC9	CCDC190	Q86UF4	675
KLHDC9	ARHGAP30	Q7Z6I6	583
KLHDC9	SLAMF8	Q9P0V8	535
KLHDC9	PROCA1	Q8NCQ7	495
KLHDC9	GPS2	Q13227	456
KLHDC9	NECTIN4	Q96NY8	450
KLHDC9	INCA1	Q0VD86	446
KLHDC9	ALOXE3	Q9BYJ1	436
KLHDC9	CCDC74B	Q96LY2	419
KLHDC9	XRCC6	P12956	419
KLHDC9	CCDC181	Q5TID7	419
KLHDC9	CCDC169	A6NNP5	414
KLHDC9	ITGB6	P18564	393
KLHDC9	AMDHD1	Q96NU7	386
KLHDC9	SLC66A3	Q8N755	372

IntAct

8 interactions, top by confidence:

A	B	Type	Score
GLRX3	KLHDC9	psi-mi:“MI:0915”(physical association)	0.560
KLHDC9	CTSA	psi-mi:“MI:0914”(association)	0.350
CEACAM8	HS3ST1	psi-mi:“MI:0914”(association)	0.350
KLHDC9	GLRX3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): GLB1 (Affinity Capture-MS), CTSA (Affinity Capture-MS), THOC3 (Affinity Capture-MS), NT5DC2 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), KLHDC9 (Two-hybrid), KLHDC9 (Two-hybrid), KLHDC9 (Negative Genetic), GLB1 (Affinity Capture-MS), THOC3 (Affinity Capture-MS), NT5DC2 (Affinity Capture-MS), CTSA (Affinity Capture-MS), KLHDC9 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A5PKD8, A6NED2, A8MQ27, O35465, O60294, O75808, O94819, O95382, P70268, Q0MW30, Q14318, Q16512, Q2T9J0, Q32NY4, Q32P44, Q3B7U9, Q3MHW0, Q3U5Q7, Q3USL1, Q4R828, Q561R2, Q5EBM0, Q5EBP3, Q5PQP9, Q60806, Q63433, Q6PAT0, Q7T0L4, Q8BNW9, Q8BTU7, Q8BYR1, Q8IYL2, Q8N5A5, Q8NEP7, Q8VC03, Q8VHS5, Q8WXI3, Q91ZT7, Q96C12

Diamond homologs: Q3USL1, Q8NEP7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

522 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161099470:G:GT	donor_gain	0.9900
1:161099797:G:GG	donor_gain	0.9900
1:161099017:G:GT	donor_gain	0.9700
1:161099451:T:TA	donor_gain	0.9700
1:161099059:ATTGG:A	donor_loss	0.9600
1:161099060:TTGGT:T	donor_loss	0.9600
1:161099061:TGG:T	donor_loss	0.9600
1:161099063:GTAT:G	donor_loss	0.9600
1:161099064:T:A	donor_loss	0.9600
1:161100078:T:TA	acceptor_gain	0.9600
1:161099344:A:AG	acceptor_gain	0.9500
1:161099345:G:GG	acceptor_gain	0.9500
1:161099792:TACTC:T	donor_gain	0.9500
1:161099434:C:G	donor_gain	0.9400
1:161098712:G:GA	donor_gain	0.9300
1:161099501:TTAAG:T	donor_loss	0.9300
1:161099502:TAAG:T	donor_loss	0.9300
1:161099503:AAG:A	donor_loss	0.9300
1:161099504:AGGT:A	donor_loss	0.9300
1:161099505:GGT:G	donor_loss	0.9300
1:161099506:GTATT:G	donor_loss	0.9300
1:161099507:T:G	donor_loss	0.9300
1:161099596:A:G	acceptor_gain	0.9300
1:161099063:G:GG	donor_gain	0.9200
1:161099428:C:A	donor_gain	0.9200
1:161099429:A:AG	donor_gain	0.9100
1:161099447:G:GT	donor_gain	0.8800
1:161098481:T:G	donor_gain	0.8700
1:161098711:T:TA	donor_gain	0.8700
1:161099065:A:C	donor_loss	0.8700

AlphaMissense

2232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161099734:G:T	G275V	0.967
1:161098623:T:C	F30L	0.966
1:161098625:C:A	F30L	0.966
1:161098625:C:G	F30L	0.966
1:161099730:T:C	F274L	0.965
1:161099732:T:A	F274L	0.965
1:161099732:T:G	F274L	0.965
1:161100078:T:A	W302R	0.962
1:161100078:T:C	W302R	0.962
1:161099734:G:A	G275D	0.957
1:161100153:T:G	Y327D	0.952
1:161098584:T:A	W17R	0.949
1:161098584:T:C	W17R	0.949
1:161098586:G:C	W17C	0.948
1:161098586:G:T	W17C	0.948
1:161099718:T:C	F270L	0.945
1:161099720:T:A	F270L	0.945
1:161099720:T:G	F270L	0.945
1:161099785:T:A	I292N	0.945
1:161099697:T:C	S263P	0.943
1:161099725:T:A	V272E	0.942
1:161099779:T:C	L290P	0.938
1:161098969:T:C	L145P	0.937
1:161100163:G:T	G330V	0.937
1:161098932:A:C	S133R	0.935
1:161098934:T:A	S133R	0.935
1:161098934:T:G	S133R	0.935
1:161099722:C:A	A271D	0.935
1:161100162:G:T	G330W	0.933
1:161099032:T:C	L166S	0.932

dbSNP variants (sampled 300 via entrez): RS1000362393 (1:161099213 T>C), RS1000473365 (1:161098841 C>A,T), RS1000766825 (1:161097524 T>C), RS1001093052 (1:161097698 C>A,G,T), RS1001370496 (1:161096879 C>A), RS1001483330 (1:161097258 C>T), RS1004722701 (1:161100125 T>TCGTG), RS1004830910 (1:161100403 C>T), RS1004834350 (1:161097987 T>C), RS1004949038 (1:161097721 T>C), RS1005168776 (1:161096406 T>A), RS1011986884 (1:161100628 A>G), RS1013564246 (1:161096798 T>C), RS1013596933 (1:161097704 C>A,T), RS1013995317 (1:161097580 T>C)

Disease associations

OMIM: gene MIM:617375 | 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
GCST003542_135	Night sleep phenotypes	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
urushiol	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MRK 003	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	increases abundance, increases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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