KCTD19

Summary

KCTD19 (potassium channel tetramerization domain containing 19, HGNC:24753) is a protein-coding gene on chromosome 16q22.1, encoding BTB/POZ domain-containing protein KCTD19 (Q17RG1). Transcription regulator which is essential for male fertility and for the completion of meiotic prophase in spermatocytes.

Predicted to enable identical protein binding activity. Predicted to be involved in male meiotic nuclear division. Predicted to be located in nucleus.

Source: NCBI Gene 146212 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 135 total — 1 likely-pathogenic
• MANE Select transcript: NM_001100915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24753
Approved symbol	KCTD19
Name	potassium channel tetramerization domain containing 19
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40162
Ensembl gene	ENSG00000168676
Ensembl biotype	protein_coding
OMIM	619943
Entrez	146212

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000304372, ENST00000561625, ENST00000562721, ENST00000562841, ENST00000562860, ENST00000566295, ENST00000566392, ENST00000567976, ENST00000568736, ENST00000569333, ENST00000570049

RefSeq mRNA: 1 — MANE Select: NM_001100915 NM_001100915

CCDS: CCDS42179

Canonical transcript exons

ENST00000304372 — 16 exons

Exon	Start	End
ENSE00001480565	67289432	67289682
ENSE00002583723	67326705	67326741
ENSE00003465170	67304421	67304571
ENSE00003486672	67320589	67320885
ENSE00003520093	67290885	67290986
ENSE00003535633	67297503	67297663
ENSE00003540842	67291646	67291837
ENSE00003543555	67296159	67296259
ENSE00003550729	67295263	67295405
ENSE00003581946	67293544	67294171
ENSE00003613962	67303146	67303337
ENSE00003646095	67294973	67295056
ENSE00003648314	67299363	67299573
ENSE00003662011	67294580	67294694
ENSE00003665591	67291309	67291463
ENSE00003686201	67301791	67301922

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 95.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3292 / max 120.4397, expressed in 124 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157763	0.2944	115
157765	0.0180	6
157762	0.0100	3
157764	0.0068	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	95.16	gold quality
left testis	UBERON:0004533	95.01	gold quality
testis	UBERON:0000473	91.46	gold quality
adult organism	UBERON:0007023	84.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.40	gold quality
upper arm skin	UBERON:0004263	75.70	gold quality
kidney epithelium	UBERON:0004819	68.21	gold quality
vastus lateralis	UBERON:0001379	67.00	gold quality
quadriceps femoris	UBERON:0001377	66.58	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.56	gold quality
left ventricle myocardium	UBERON:0006566	66.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.64	gold quality
ventricular zone	UBERON:0003053	64.97	gold quality
biceps brachii	UBERON:0001507	64.30	gold quality
nasal cavity epithelium	UBERON:0005384	63.74	gold quality
sperm	CL:0000019	62.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	61.69	gold quality
stromal cell of endometrium	CL:0002255	60.82	gold quality
putamen	UBERON:0001874	60.68	gold quality
decidua	UBERON:0002450	60.11	gold quality
islet of Langerhans	UBERON:0000006	60.07	gold quality
muscle tissue	UBERON:0002385	59.06	gold quality
adrenal tissue	UBERON:0018303	59.05	gold quality
deltoid	UBERON:0001476	58.84	gold quality
skeletal muscle tissue	UBERON:0001134	58.29	gold quality
caudate nucleus	UBERON:0001873	58.25	gold quality
layer of synovial tissue	UBERON:0007616	58.22	gold quality
sural nerve	UBERON:0015488	58.08	silver quality
substantia nigra pars compacta	UBERON:0001965	57.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.70

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Biallelic variants in KCTD19 associated with male factor infertility and oligoasthenoteratozoospermia. (PMID:37192818)
• Homozygous nonsense variants of KCTD19 cause male infertility in humans and mice. (PMID:37257643)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kctd19	ENSMUSG00000051648
rattus_norvegicus	Kctd19	ENSRNOG00000016760
drosophila_melanogaster	twz	FBGN0034636
caenorhabditis_elegans	F32B4.5	WBGENE00009315

Paralogs (13): KCTD1 (ENSG00000134504), KCTD14 (ENSG00000151364), KCTD15 (ENSG00000153885), KCTD18 (ENSG00000155729), KCTD6 (ENSG00000168301), KCTD12 (ENSG00000178695), KCTD4 (ENSG00000180332), KCTD16 (ENSG00000183775), KCTD8 (ENSG00000183783), KCTD21 (ENSG00000188997), KCNRG (ENSG00000198553), KCTD11 (ENSG00000213859), KCTD7 (ENSG00000243335)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD19 — Q17RG1 (reviewed: Q17RG1)

Alternative names: Potassium channel tetramerization domain-containing protein 19

All UniProt accessions (5): Q17RG1, H3BVC0, J3KRQ9, J3KSZ9, J3QKV2

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator which is essential for male fertility and for the completion of meiotic prophase in spermatocytes. Regulates progression of the pachytene stage of meiotic prophase and promotes the transcriptional activation activity ZNF541. Required for the organization of chromosomes during metaphase I.

Subunit / interactions. Identified in a complex with ZNF541, HDAC1 and HSPA2. Identified in a complex with ZNF541 and HDAC1. Identified in a complex with HDAC1, HDAC2, DNTTIP1 and ZNF541.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001094385* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily

Pfam: PF02214

UniProt features (8 total): domain 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q17RG1-F1	66.53	0.31

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 (1): 270

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): chr16q22, GOBP_MALE_GAMETE_GENERATION, GOBP_ORGANELLE_FISSION, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_MEIOTIC_CELL_CYCLE, GOBP_CELL_CYCLE_PROCESS, GOBP_MALE_MEIOTIC_NUCLEAR_DIVISION, GOBP_PROTEIN_COMPLEX_OLIGOMERIZATION, ZNF2_TARGET_GENES, ZNF274_TARGET_GENES, ZNF512_TARGET_GENES, ZNF843_TARGET_GENES, GSE7568_IL4_VS_IL4_AND_DEXAMETHASONE_TREATED_MACROPHAGE_DN

GO Biological Process (5): male meiotic nuclear division (GO:0007140), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), protein homooligomerization (GO:0051260), meiotic cell cycle (GO:0051321)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
male gamete generation	2
meiotic nuclear division	2
meiotic cell cycle	1
developmental process involved in reproduction	1
cellular developmental process	1
protein complex oligomerization	1
cell cycle	1
sexual reproduction	1
reproductive process	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3197 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD19	DNTTIP1	Q9H147	664
KCTD19	KCTD3	Q9Y597	645
KCTD19	KCTD20	Q7Z5Y7	643
KCTD19	BTBD10	Q9BSF8	641
KCTD19	SHKBP1	Q8TBC3	615
KCTD19	KCTD18	Q6PI47	603
KCTD19	PLEKHG4	Q58EX7	585
KCTD19	HDAC1	Q13547	558
KCTD19	MIDEAS	Q6PJG2	547
KCTD19	TNFAIP1	Q13829	541
KCTD19	MEIKIN	A0A087WXM9	535
KCTD19	KCTD8	Q6ZWB6	533
KCTD19	HSPA2	P54652	529
KCTD19	KCTD5	Q9NXV2	515
KCTD19	KCTD9	Q7L273	514

IntAct

9 interactions, top by confidence:

A	B	Type	Score
KCTD19		psi-mi:“MI:0915”(physical association)	0.560
	KCTD19	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN22	KCTD19	psi-mi:“MI:0915”(physical association)	0.560
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
KCTD19	ECT2L	psi-mi:“MI:0914”(association)	0.350
KCTD19	ZSCAN22	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): KCTD19 (Two-hybrid), ZSCAN22 (Two-hybrid), ECT2L (Affinity Capture-MS), KCTD15 (Affinity Capture-MS), KCTD19 (Affinity Capture-MS), KCTD19 (Affinity Capture-MS), KCTD19 (Affinity Capture-MS), KCTD19 (Affinity Capture-MS)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A7YWH3, B1WBU4, O15151, O35618, O43298, O88850, P24278, P97303, Q01954, Q0V8G8, Q15916, Q17RG1, Q562E2, Q5RC05, Q5RDQ6, Q5SXH7, Q5TC79, Q5VYS8, Q5W0Q7, Q5XIN1, Q6ZPY5, Q6ZSB9, Q6ZU67, Q7ZUW7, Q7ZYI3, Q8BLK9, Q8BSV3, Q8IW35, Q8K088, Q8N680, Q8N7W2, Q8TCN5, Q8VHI4, Q8WW38, Q90W33, Q96BR9, Q96S38, Q99ME3

Diamond homologs: A3KMV1, A4IFB4, A5PKG7, A6H6X4, A7YWH3, A9ULR9, B1WC97, B5DEL1, D5SHR0, O70479, O88759, P0C5J9, P15388, P17971, P25122, P48547, P59994, P59995, Q03607, Q03719, Q09389, Q0VD00, Q0VFV7, Q13829, Q14681, Q17RG1, Q28DC9, Q2HJ48, Q2T9W0, Q2TUM3, Q3URF8, Q4G0X4, Q50H33, Q52PG9, Q54KH0, Q562E2, Q58DF7, Q5DTY9, Q5F3E8, Q5M956

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	114
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
224816	NM_001100915.3(KCTD19):c.215C>A (p.Thr72Asn)	Likely pathogenic

SpliceAI

2903 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67291461:CTT:C	acceptor_gain	1.0000
16:67291464:C:CC	acceptor_gain	1.0000
16:67294574:GCTT:G	donor_loss	1.0000
16:67294578:A:AC	donor_gain	1.0000
16:67294578:AC:A	donor_loss	1.0000
16:67294578:ACTT:A	donor_gain	1.0000
16:67294579:C:CT	donor_gain	1.0000
16:67294579:CT:C	donor_gain	1.0000
16:67294579:CTT:C	donor_gain	1.0000
16:67294579:CTTC:C	donor_gain	1.0000
16:67294579:CTTCT:C	donor_gain	1.0000
16:67294581:T:TA	donor_gain	1.0000
16:67294642:T:TA	donor_gain	1.0000
16:67294690:ATGAC:A	acceptor_gain	1.0000
16:67294691:TGAC:T	acceptor_gain	1.0000
16:67294692:GAC:G	acceptor_gain	1.0000
16:67294693:AC:A	acceptor_gain	1.0000
16:67294693:ACC:A	acceptor_loss	1.0000
16:67294694:CC:C	acceptor_gain	1.0000
16:67294694:CCTG:C	acceptor_loss	1.0000
16:67294695:C:CC	acceptor_gain	1.0000
16:67294696:T:A	acceptor_loss	1.0000
16:67294705:C:T	acceptor_gain	1.0000
16:67294971:A:AC	donor_gain	1.0000
16:67294972:C:CC	donor_gain	1.0000
16:67297498:CTTA:C	donor_gain	1.0000
16:67297501:A:AC	donor_gain	1.0000
16:67297502:C:CC	donor_gain	1.0000
16:67297502:CTGAG:C	donor_gain	1.0000
16:67299361:A:AC	donor_gain	1.0000

AlphaMissense

6053 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67320605:A:G	L95P	0.999
16:67320621:C:G	A90P	0.999
16:67320812:A:T	V26D	0.999
16:67295296:C:G	R453T	0.998
16:67303203:A:G	W196R	0.998
16:67303203:A:T	W196R	0.998
16:67320680:A:G	L70P	0.998
16:67320684:A:C	Y69D	0.998
16:67320701:A:G	F63S	0.998
16:67320710:C:T	G60D	0.998
16:67320714:C:G	D59H	0.998
16:67320817:G:C	F24L	0.998
16:67320817:G:T	F24L	0.998
16:67320819:A:G	F24L	0.998
16:67320830:C:T	G20E	0.998
16:67320831:C:A	G20W	0.998
16:67320839:A:G	F17S	0.998
16:67295295:T:A	R453S	0.997
16:67295295:T:G	R453S	0.997
16:67304567:A:G	L102P	0.997
16:67320596:A:G	L98S	0.997
16:67320700:A:C	F63L	0.997
16:67320700:A:T	F63L	0.997
16:67320702:A:G	F63L	0.997
16:67320713:T:A	D59V	0.997
16:67320780:A:G	S37P	0.997
16:67320818:A:G	F24S	0.997
16:67295052:A:G	W466R	0.996
16:67295052:A:T	W466R	0.996
16:67295304:G:C	N450K	0.996

dbSNP variants (sampled 300 via entrez): RS1000129864 (16:67289884 C>T), RS1000217128 (16:67299927 C>T), RS1000297597 (16:67324985 G>C), RS1000314267 (16:67303931 T>C), RS1000428926 (16:67303533 C>G), RS1000482306 (16:67295276 G>A), RS1000588618 (16:67318997 T>G), RS1000625039 (16:67294753 G>A,T), RS1000694982 (16:67296415 T>G), RS1000790994 (16:67308179 T>C), RS1000879868 (16:67309964 A>G), RS1000885876 (16:67307623 A>G), RS1001168679 (16:67317628 A>G), RS1001181530 (16:67300306 G>T), RS1001281986 (16:67325775 A>G)

Disease associations

OMIM: gene MIM:619943 | 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
GCST004063_120	Waist circumference adjusted for body mass index	2.000000e-08
GCST004063_121	Waist circumference adjusted for body mass index	5.000000e-06
GCST004500_115	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	8.000000e-11
GCST004500_73	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	7.000000e-09
GCST004501_98	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-11
GCST004501_99	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-09
GCST004504_70	Waist circumference adjusted for BMI in non-smokers	5.000000e-09
GCST004504_71	Waist circumference adjusted for BMI in non-smokers	9.000000e-07
GCST008158_46	Body mass index	1.000000e-06
GCST010002_113	Refractive error	2.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
entinostat	increases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Tretinoin	increases expression	1
Asbestos, Crocidolite	affects methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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