KLHDC7A

Summary

KLHDC7A (kelch domain containing 7A, HGNC:26791) is a protein-coding gene on chromosome 1p36.13, encoding Kelch domain-containing protein 7A (Q5VTJ3).

Predicted to be located in membrane.

Source: NCBI Gene 127707 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 145 total
• MANE Select transcript: NM_152375

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26791
Approved symbol	KLHDC7A
Name	kelch domain containing 7A
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38753
Ensembl gene	ENSG00000179023
Ensembl biotype	protein_coding
Entrez	127707

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000400664

RefSeq mRNA: 1 — MANE Select: NM_152375 NM_152375

CCDS: CCDS185

Canonical transcript exons

ENST00000400664 — 1 exons

Exon	Start	End
ENSE00001544128	18480930	18485974

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 86.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4321 / max 40.0063, expressed in 160 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1031	0.2823	112
1029	0.0882	39
1030	0.0350	13
1032	0.0265	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	86.75	gold quality
oocyte	CL:0000023	82.23	gold quality
adult mammalian kidney	UBERON:0000082	81.29	gold quality
bronchial epithelial cell	CL:0002328	80.82	gold quality
metanephros cortex	UBERON:0010533	80.60	gold quality
nasal cavity epithelium	UBERON:0005384	79.22	gold quality
bronchus	UBERON:0002185	79.02	gold quality
palpebral conjunctiva	UBERON:0001812	78.69	gold quality
kidney	UBERON:0002113	78.39	gold quality
renal medulla	UBERON:0000362	77.19	gold quality
cortex of kidney	UBERON:0001225	74.09	gold quality
metanephros	UBERON:0000081	70.49	gold quality
right lobe of liver	UBERON:0001114	67.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.58	gold quality
esophagus squamous epithelium	UBERON:0006920	66.30	gold quality
liver	UBERON:0002107	66.28	gold quality
adult organism	UBERON:0007023	65.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	64.72	gold quality
body of pancreas	UBERON:0001150	64.46	gold quality
lower lobe of lung	UBERON:0008949	64.08	silver quality
epithelium of nasopharynx	UBERON:0001951	63.95	silver quality
urinary bladder	UBERON:0001255	62.88	gold quality
pancreas	UBERON:0001264	61.40	gold quality
body of stomach	UBERON:0001161	60.71	gold quality
nasal cavity mucosa	UBERON:0001826	60.50	gold quality
buccal mucosa cell	CL:0002336	60.22	gold quality
pigmented layer of retina	UBERON:0001782	59.77	silver quality
gall bladder	UBERON:0002110	59.41	gold quality
stomach	UBERON:0000945	58.45	gold quality
mucosa of transverse colon	UBERON:0004991	58.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting KLHDC7A, 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-150-5P	99.99	66.69	1976
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4641	99.28	66.64	744

Literature-anchored findings (GeneRIF, showing 1)

• Results suggest that LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms influence the development of diabetic retinopathy (DR). (PMID:27607899)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhdc7a	ENSDARG00000105322
mus_musculus	Klhdc7a	ENSMUSG00000078234
rattus_norvegicus	Klhdc7a	ENSRNOG00000018867

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch domain-containing protein 7A — Q5VTJ3 (reviewed: Q5VTJ3)

All UniProt accessions (1): Q5VTJ3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_689588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006652	Kelch_1	Repeat
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR052310	Kelch/BTB_domain_protein	Family

Pfam: PF01344

UniProt features (22 total): sequence variant 8, repeat 5, compositionally biased region 2, modified residue 2, region of interest 2, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTJ3-F1	61.91	0.33

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): 86, 365

Glycosylation sites (1): 257

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): LFA1_Q6, GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, NF1_Q6_01, IRF_Q6, HNF1_01, LEIN_CHOROID_PLEXUS_MARKERS, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_DN, KIM_MYCN_AMPLIFICATION_TARGETS_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, chr1p36, MIKKELSEN_IPS_LCP_WITH_H3K4ME3, MIKKELSEN_ES_LCP_WITH_H3K4ME3, DELACROIX_RAR_BOUND_ES, IRF1_01

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHDC7A	KLHDC10	Q6PID8	486
KLHDC7A	PPM1J	Q5JR12	432
KLHDC7A	SLC25A45	Q8N413	412
KLHDC7A	IGSF21	Q96ID5	395
KLHDC7A	C1orf50	Q9BV19	393
KLHDC7A	PLEKHD1	A6NEE1	378
KLHDC7A	PIDD1	Q9HB75	376
KLHDC7A	C21orf58	P58505	370
KLHDC7A	ANKRD34A	Q69YU3	368
KLHDC7A	INKA2	Q9NTI7	364
KLHDC7A	FAM124A	Q86V42	348
KLHDC7A	MRPS30	Q9NP92	348
KLHDC7A	CITED4	Q96RK1	342
KLHDC7A	ZNF404	Q494X3	336
KLHDC7A	FLACC1	Q96Q35	333

IntAct

108 interactions, top by confidence:

A	B	Type	Score
KLHDC7A	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SNTB1	KLHDC7A	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	GOPC	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
WHRN	KLHDC7A	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF12	KLHDC7A	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
GRID2IP	KLHDC7A	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
KLHDC7A	TJP1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (2): KLHDC7A (Proximity Label-MS), KLHDC7A (Proximity Label-MS)

ESM2 similar proteins: A0A0U1RR11, A0A0U1RRI6, A6NCS6, A6NJG2, B0BN44, D3YXK1, E9PY61, E9Q0B3, F5H4A9, O00220, O00221, P09038, P0DPI3, P22083, P98077, Q08AU9, Q2M2W7, Q2M3V2, Q2TBI2, Q5F267, Q5FW56, Q5IS69, Q5R866, Q5T4W7, Q5TM52, Q5U4P2, Q5VTJ3, Q659K9, Q673H1, Q69ZB3, Q6AYE8, Q6IPT2, Q6PJ61, Q7RTU4, Q7TSX9, Q7YR31, Q80SU3, Q86SH2, Q86Y97, Q8NBR0

Diamond homologs: A2APT9, A6NCF5, C9JR72, O94819, Q2T9Z7, Q5R866, Q5RDY3, Q5VTJ3, Q5ZLD3, Q6PF15, Q6ZPT1, Q8BFQ9, Q8BGY4, Q8BNW9, Q8C3F7, Q8C828, Q920Q8, Q96G42, Q9P2J3, Q9P2K6, Q25386, Q3ZB90, Q5U575, Q6GQU2, Q9C6Z0, Q9SVA0, A0A1B8YAB1, A6QQY2, O82374, O82378, Q3B7M1, Q5RCQ9, Q80TF4, Q8N239, Q8N4N3, Q8NBE8, Q9P2N7, D4A2K4, G3X9X1, O35709

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Ras activation upon Ca2+ influx through NMDA receptor	5	54.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	52.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	52.3×	1e-06
Long-term potentiation	5	45.8×	2e-06
Assembly and cell surface presentation of NMDA receptors	8	39.0×	2e-09
Neurexins and neuroligins	9	34.1×	8e-10
Protein-protein interactions at synapses	5	25.5×	4e-05
RHOB GTPase cycle	5	14.8×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	81.8×	9e-15
protein localization to synapse	6	64.7×	4e-08
receptor clustering	7	61.5×	4e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	48.9×	1e-08
protein-containing complex assembly	9	14.4×	8e-07
cell-cell adhesion	10	14.3×	2e-07
protein localization to plasma membrane	5	7.7×	8e-03
chemical synaptic transmission	7	7.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

483 predictions. Top by Δscore:

Variant	Effect	Δscore
1:18481075:ACT:A	donor_gain	0.9500
1:18481076:C:G	donor_gain	0.9400
1:18481326:G:GT	donor_gain	0.9400
1:18481464:G:A	acceptor_gain	0.9400
1:18481463:T:TA	acceptor_gain	0.9300
1:18481088:GGCT:G	donor_gain	0.9100
1:18481089:GCTG:G	donor_gain	0.9100
1:18481268:GCT:G	donor_gain	0.9000
1:18481044:G:GA	donor_gain	0.8900
1:18481043:T:TA	donor_gain	0.8700
1:18481276:A:T	donor_gain	0.8300
1:18481469:GC:G	acceptor_gain	0.8200
1:18481093:TAC:T	donor_gain	0.8100
1:18481094:ACA:A	donor_gain	0.8100
1:18484380:A:T	donor_gain	0.8000
1:18481286:GCCCC:G	donor_gain	0.7600
1:18482252:CAG:C	acceptor_gain	0.7500
1:18482253:A:T	acceptor_gain	0.7500
1:18482254:G:T	acceptor_gain	0.7500
1:18483985:T:A	acceptor_gain	0.7500
1:18484142:GATCT:G	acceptor_gain	0.7500
1:18483983:ATT:A	acceptor_gain	0.7400
1:18484379:G:GT	donor_gain	0.7300
1:18481459:C:CA	acceptor_gain	0.7200
1:18483089:ACG:A	donor_gain	0.7100
1:18481156:G:GT	donor_gain	0.7000
1:18481344:CTCAG:C	donor_loss	0.7000
1:18481345:TCAG:T	donor_loss	0.7000
1:18481346:CAGG:C	donor_loss	0.7000
1:18481347:AG:A	donor_loss	0.7000

AlphaMissense

4986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:18482686:T:A	W569R	0.988
1:18482686:T:C	W569R	0.988
1:18482817:G:C	W612C	0.982
1:18482817:G:T	W612C	0.982
1:18482533:T:A	W518R	0.981
1:18482533:T:C	W518R	0.981
1:18482815:T:A	W612R	0.980
1:18482815:T:C	W612R	0.980
1:18483188:T:C	F736S	0.979
1:18482688:G:C	W569C	0.977
1:18482688:G:T	W569C	0.977
1:18483025:T:C	F682L	0.977
1:18483027:T:A	F682L	0.977
1:18483027:T:G	F682L	0.977
1:18483214:T:C	F745L	0.975
1:18483216:T:A	F745L	0.975
1:18483216:T:G	F745L	0.975
1:18483026:T:C	F682S	0.972
1:18482535:G:C	W518C	0.970
1:18482535:G:T	W518C	0.970
1:18482608:T:C	F543L	0.970
1:18482610:C:A	F543L	0.970
1:18482610:C:G	F543L	0.970
1:18482600:A:T	N540I	0.969
1:18482848:T:C	F623L	0.966
1:18482850:C:A	F623L	0.966
1:18482850:C:G	F623L	0.966
1:18483085:T:A	W702R	0.966
1:18483085:T:C	W702R	0.966
1:18482759:C:A	A593D	0.962

dbSNP variants (sampled 300 via entrez): RS1000019759 (1:18480349 C>T), RS1000104976 (1:18480050 C>G), RS1000984564 (1:18485444 G>C), RS1001055590 (1:18484763 A>G), RS1002437734 (1:18480476 T>C), RS1002742662 (1:18486293 T>C), RS1005425370 (1:18479172 C>T), RS1005456628 (1:18479441 T>A,C), RS1005622459 (1:18483916 C>A), RS1005724223 (1:18483494 C>G,T), RS1005876876 (1:18479539 A>G), RS1005895016 (1:18479714 C>G,T), RS1006028497 (1:18484681 C>A), RS1006473946 (1:18484923 G>A), RS1007135232 (1:18483861 G>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001017_5	Diabetic retinopathy	5.000000e-06
GCST002830_23	Urate levels in lean individuals	9.000000e-06
GCST003225_17	Pelvic organ prolapse (moderate/severe)	9.000000e-06
GCST004988_656	Breast cancer	2.000000e-15
GCST006612_123	LDL cholesterol	5.000000e-09
GCST008058_102	Estimated glomerular filtration rate	1.000000e-18
GCST008059_91	Estimated glomerular filtration rate	2.000000e-19
GCST008745_84	Estimated glomerular filtration rate in non-diabetics	5.000000e-08
GCST008747_106	Estimated glomerular filtration rate	2.000000e-09
GCST90013407_171	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

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
Valproic Acid	decreases expression, increases methylation, affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	increases expression	1
sodium arsenite	affects expression	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases methylation	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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