CATIP

Summary

CATIP (ciliogenesis associated TTC17 interacting protein, HGNC:25062) is a protein-coding gene on chromosome 2q35, encoding Ciliogenesis-associated TTC17-interacting protein (Q7Z7H3). Plays a role in primary ciliogenesis by modulating actin polymerization.

Involved in actin filament polymerization and cilium organization. Located in several cellular components, including actin cytoskeleton; nucleus; and plasma membrane. Implicated in spermatogenic failure 54.

Source: NCBI Gene 375307 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 56 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 10 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 17
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.14 (unconstrained)
• MANE Select transcript: NM_198559
• Notable: 56 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25062
Approved symbol	CATIP
Name	ciliogenesis associated TTC17 interacting protein
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	MGC50811
Ensembl gene	ENSG00000158428
Ensembl biotype	protein_coding
OMIM	619387
Entrez	375307

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000289388

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 3

ENST00000289388, ENST00000480532, ENST00000481940, ENST00000494447, ENST00000495773, ENST00000715906, ENST00000715907, ENST00000851693, ENST00000851694, ENST00000851695, ENST00000851696, ENST00001139129

RefSeq mRNA: 2 — MANE Select: NM_198559 NM_001320865, NM_198559

CCDS: CCDS2414

Canonical transcript exons

ENST00000289388 — 10 exons

Exon	Start	End
ENSE00001038842	218357534	218357734
ENSE00001074994	218358037	218358092
ENSE00001074995	218364628	218364752
ENSE00001075001	218362735	218362902
ENSE00001339360	218357095	218357187
ENSE00001339369	218356857	218356909
ENSE00001869443	218367722	218368094
ENSE00003507596	218360573	218360659
ENSE00003562236	218367430	218367518
ENSE00003637600	218367024	218367100

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 95.62.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1955 / max 9.7597, expressed in 108 samples.

Highest expression (Bgee): uterine tube, olfactory segment of nasal mucosa, fallopian tube, lobe of thyroid gland, thyroid gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CATIP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	6.7e-22	-0.38	2:218363885:C:T
Thyroid	eqtl	9.6e-14	-0.25	2:218357123:G:A
Testis	sqtl	9.2e-11	+0.60	2:218357123:G:A
Thyroid	sqtl	1.9e-04	+0.36	2:218357123:G:A
Spleen	eqtl	1.6e-03	-0.25	2:218343254:A:G
Brain Caudate basal ganglia	eqtl	5.0e-03	-0.18	2:218203057:C:T
Brain Anterior cingulate cortex BA24	eqtl	6.9e-03	-0.77	2:218334281:T:C
Brain Putamen basal ganglia	eqtl	1.1e-02	+0.32	2:218356632:A:T
Testis	eqtl	1.9e-02	-0.24	2:217880754:G:T
Brain Cerebellum	eqtl	2.8e-02	+0.36	2:218356632:A:T
Pituitary	eqtl	3.0e-02	-0.21	2:219047907:A:G
Esophagus Gastroesophageal Junction	eqtl	4.4e-02	-0.85	2:217872547:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
25314	0.1482	84
25313	0.0472	23

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.63	gold quality
fallopian tube	UBERON:0003889	80.48	gold quality
right lobe of thyroid gland	UBERON:0001119	76.80	gold quality
thyroid gland	UBERON:0002046	75.82	gold quality
left lobe of thyroid gland	UBERON:0001120	75.39	gold quality
blood	UBERON:0000178	74.90	gold quality
adult mammalian kidney	UBERON:0000082	74.73	gold quality
monocyte	CL:0000576	74.35	gold quality
right lung	UBERON:0002167	74.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.78	gold quality
leukocyte	CL:0000738	73.74	gold quality
left testis	UBERON:0004533	73.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.89	gold quality
granulocyte	CL:0000094	72.83	gold quality
testis	UBERON:0000473	72.67	gold quality
right testis	UBERON:0004534	72.33	gold quality
kidney	UBERON:0002113	70.82	gold quality
metanephros cortex	UBERON:0010533	70.57	gold quality
left uterine tube	UBERON:0001303	70.07	gold quality
adenohypophysis	UBERON:0002196	69.95	gold quality
upper lobe of left lung	UBERON:0008952	68.38	gold quality
pituitary gland	UBERON:0000007	68.37	gold quality
cortex of kidney	UBERON:0001225	66.76	gold quality
lung	UBERON:0002048	65.91	gold quality
placenta	UBERON:0001987	65.39	gold quality
prostate gland	UBERON:0002367	64.27	gold quality
body of pancreas	UBERON:0001150	63.92	gold quality
bone marrow	UBERON:0002371	63.64	gold quality
bone marrow cell	CL:0002092	63.51	silver quality
caudate nucleus	UBERON:0001873	63.05	gold quality
hypothalamus	UBERON:0001898	62.48	gold quality
endocervix	UBERON:0000458	62.28	gold quality
spleen	UBERON:0002106	62.13	gold quality
pancreas	UBERON:0001264	61.46	gold quality
Ammon’s horn	UBERON:0001954	57.25	gold quality
islet of Langerhans	UBERON:0000006	57.19	gold quality
gall bladder	UBERON:0002110	57.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	57.09	gold quality
left ovary	UBERON:0002119	57.08	gold quality
temporal lobe	UBERON:0001871	56.43	gold quality
left adrenal gland	UBERON:0001234	56.40	gold quality
amygdala	UBERON:0001876	56.38	gold quality
nucleus accumbens	UBERON:0001882	56.38	gold quality
right adrenal gland cortex	UBERON:0035827	56.33	gold quality
substantia nigra	UBERON:0002038	56.29	gold quality
ovary	UBERON:0000992	56.28	gold quality
myometrium	UBERON:0001296	56.23	gold quality
left adrenal gland cortex	UBERON:0035825	55.80	gold quality
right adrenal gland	UBERON:0001233	55.13	gold quality
adrenal gland	UBERON:0002369	55.06	gold quality
body of stomach	UBERON:0001161	54.73	gold quality
right ovary	UBERON:0002118	54.44	gold quality
body of uterus	UBERON:0009853	54.31	gold quality
uterine cervix	UBERON:0000002	53.77	gold quality
stomach	UBERON:0000945	53.30	gold quality
smooth muscle tissue	UBERON:0001135	52.86	gold quality
liver	UBERON:0002107	52.84	gold quality
right lobe of liver	UBERON:0001114	52.16	gold quality
vermiform appendix	UBERON:0001154	52.02	gold quality
material anatomical entity	UBERON:0000465	51.83	gold quality
multicellular organism	UBERON:0000468	51.83	gold quality
anatomical system	UBERON:0000467	51.80	gold quality
fundus of stomach	UBERON:0001160	51.61	gold quality
brain	UBERON:0000955	51.31	gold quality
omental fat pad	UBERON:0010414	51.31	gold quality
putamen	UBERON:0001874	51.25	gold quality
endometrium	UBERON:0001295	50.53	gold quality
descending thoracic aorta	UBERON:0002345	50.22	gold quality
adrenal tissue	UBERON:0018303	49.92	gold quality
adipose tissue	UBERON:0001013	49.90	gold quality
ectocervix	UBERON:0012249	49.90	gold quality
apex of heart	UBERON:0002098	49.55	gold quality
subcutaneous adipose tissue	UBERON:0002190	48.73	gold quality
thoracic mammary gland	UBERON:0005200	48.48	gold quality
thoracic aorta	UBERON:0001515	48.40	gold quality
urinary bladder	UBERON:0001255	48.18	gold quality
ascending aorta	UBERON:0001496	48.15	gold quality
left coronary artery	UBERON:0001626	47.85	gold quality
tonsil	UBERON:0002372	47.54	silver quality
anterior cingulate cortex	UBERON:0009835	47.28	gold quality
right atrium auricular region	UBERON:0006631	47.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	46.79	gold quality
mucosa of transverse colon	UBERON:0004991	46.75	gold quality
cerebral cortex	UBERON:0000956	46.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	46.01	gold quality
prefrontal cortex	UBERON:0000451	45.56	gold quality
right coronary artery	UBERON:0001625	45.51	gold quality
lymph node	UBERON:0000029	45.42	gold quality
vagina	UBERON:0000996	45.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	45.07	gold quality
frontal cortex	UBERON:0001870	44.93	gold quality
lower esophagus	UBERON:0013473	44.72	gold quality
lower esophagus muscularis layer	UBERON:0035833	44.68	gold quality
heart	UBERON:0000948	44.58	gold quality
right frontal lobe	UBERON:0002810	44.49	gold quality
lower esophagus mucosa	UBERON:0035834	44.47	silver quality
colon	UBERON:0001155	44.35	gold quality
intestine	UBERON:0000160	44.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	43.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.32

HPA expression

RNA tissue specificity: Tissue enhanced

55 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Fallopian tube	tissue	18.9	high
Choroid plexus	tissue	11.6	low
Periaqueductal gray	tissue	10.2
Epididymis	tissue	4.6	not detected
Hypothalamus	tissue	4.4
Septum	tissue	4.2
Testis	tissue	3.7	low
Basal ganglia	tissue	3.5	not detected
Pons	tissue	3.3
Hippocampal formation	tissue	3.1
Superior colliculi	tissue	2.8
Medulla oblongata	tissue	2.7
Thalamus	tissue	2.6
Cerebellum	tissue	2.4	not detected
Kidney	tissue	2.3	low
Parathyroid gland	tissue	1.7	not detected
Thyroid gland	tissue	1.7	not detected
Ventral forebrain	tissue	1.7
Amygdala	tissue	1.5
Lung	tissue	1.5	not detected
Olfactory bulb	tissue	1.5
Midbrain	tissue	1.4
Pituitary gland	tissue	1.3
Corpus callosum	tissue	1.2
Pancreas	tissue	1.1	not detected
Substantia nigra	tissue	1.1
Seminal vesicle	tissue	1.0	not detected
Caudate putamen	tissue	0.9
Placenta	tissue	0.8	not detected
Locus coeruleus	tissue	0.8
Frontal cortex	tissue	0.7
Nucleus accumbens	tissue	0.7
Putamen	tissue	0.6
Spinal cord	tissue	0.6
Prostate	tissue	0.6	not detected
Entorhinal cortex	tissue	0.6
Cervix	tissue	0.5	not detected
Prefrontal cortex	tissue	0.5
Cerebral cortex	tissue	0.5	not detected
Retrosplenial cortex	tissue	0.5
Temporal cortex	tissue	0.5
Endometrium 1	tissue	0.4	low
Hippocampus	tissue	0.4	not detected
Retrosplenial and cingulate cortex	tissue	0.4
Occipital cortex	tissue	0.4
Insular cortex	tissue	0.4
Motor cortex	tissue	0.3
Gallbladder	tissue	0.3	not detected
Somatosensory cortex	tissue	0.3
Retina	tissue	0.1
Spleen	tissue	0.1	not detected
Adrenal gland	tissue	0.1	medium
Bone marrow	tissue	0.1	not detected
Nasopharynx	tissue	-1.0	medium
Bronchus	tissue	-1.0	high

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Periaquaductal grey, lateral (6.4), Nucleus tractus solitarii (5.0), Cervical spinal cord, central gray (4.7), Dorsal raphe nucleus (4.2), Periaquaductal grey, dorsal (4.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CATIP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

2 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-3189-5P	97.55	66.71	655

Functional genomics

gnomAD constraint: pLI 2.43e-11, LOEUF 1.14, missense Z 0.261 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000289388 — one region, missense o/e 0.99.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	catip	ENSDARG00000063009
mus_musculus	Catip	ENSMUSG00000073650
rattus_norvegicus	Catip	ENSRNOG00000037835

Paralogs (1): BAMBI (ENSG00000095739)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685062) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
male infertility	1
increased mean platelet volume	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	Q0IHI3	50.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR6810	ncRNA	102466197
CATIP-AS2	ncRNA	103689911
PNKD	protein-coding	25953
MIR26B	ncRNA	407017
CTDSP1	protein-coding	58190
SLC11A1	protein-coding	6556
CATIP-AS1	ncRNA	101928513
MIR6513	ncRNA	102465256
TMBIM1	protein-coding	64114
USP37	protein-coding	57695
VIL1	protein-coding	7429
AAMP	protein-coding	14
GPBAR1	protein-coding	151306

Protein

Protein identifiers

Ciliogenesis-associated TTC17-interacting protein — Q7Z7H3 (reviewed: Q7Z7H3)

All UniProt accessions (2): A0ABB0MV25, Q7Z7H3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in primary ciliogenesis by modulating actin polymerization.

Subunit / interactions. Interacts with TTC17.

Subcellular location. Nucleus. Cytoplasm. Cell membrane. Cytoskeleton.

Tissue specificity. Strongly expressed in round and elongating spermatids, weakly in pachytene spermatocytes. Expressed in Leydig cells (at protein level). Expressed in testis, placenta, prostate and lung, and moderately in ovary and brain.

Disease relevance. Spermatogenic failure 54 (SPGF54) [MIM:619379] An autosomal recessive male infertility disorder characterized by oligoteratoasthenozoospermia. Semen analysis shows markedly reduced sperm counts and severely reduced or absent sperm motility. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CATIP family.

RefSeq proteins (2): NP_001307794, NP_940961* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR047501	DD_CATIP	Domain
IPR048777	CATIP_N	Domain

Pfam: PF21772

UniProt features (6 total): region of interest 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7H3-F1	86.37	0.64

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): connecting piece; mid piece

Antibody reliability (HPA): IH supported · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 64 (showing top): GOBP_CILIUM_ORGANIZATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_CELL_PROJECTION_ORGANIZATION, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3, SMAD4_Q6, GOBP_ACTIN_POLYMERIZATION_OR_DEPOLYMERIZATION, GOBP_PROTEIN_POLYMERIZATION, GOBP_SUPRAMOLECULAR_FIBER_ORGANIZATION, CCTNTMAGA_UNKNOWN, FOXJ2_TARGET_GENES, ZFP91_TARGET_GENES, HP_ABNORMALITY_OF_REPRODUCTIVE_SYSTEM_PHYSIOLOGY, HP_DECREASED_FERTILITY, HP_INFERTILITY, HP_OLIGOZOOSPERMIA

GO Biological Process (3): actin filament polymerization (GO:0030041), cilium organization (GO:0044782), cell projection organization (GO:0030030)

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

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), cytoskeleton (GO:0005856)

GO top-level categories

13 GO namespaces:

Category	Terms
actin polymerization or depolymerization	1
protein polymerization	1
organelle organization	1
plasma membrane bounded cell projection organization	1
cellular component organization	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1
cytoskeleton	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
actin filament polymerization	BP	direct assay
cilium organization	BP	mutant phenotype
actin cytoskeleton	CC	direct assay
cytoplasm	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 474 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CATIP	CTDSP1	Q9GZU7	565
CATIP	TPGS1	Q6ZTW0	538
CATIP	ROPN1	Q9HAT0	512
CATIP	CABYR	O75952	502
CATIP	AK8	Q96MA6	498
CATIP	VWC2L	B2RUY7	490
CATIP	FBXL13	Q8NEE6	489
CATIP	ROPN1B	Q9BZX4	485
CATIP	ZFAND2B	Q8WV99	481
CATIP	PCYT1B	Q9Y5K3	475
CATIP	RNF25	Q96BH1	468
CATIP	TEX55	Q96M34	459
CATIP	ROPN1L	Q96C74	457
CATIP	STK36	Q9NRP7	449
CATIP	TTLL4	Q14679	439

IntAct

Human interaction partners of CATIP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

16 partners by confidence:

Partner	Interaction type	MIscore	Records
KRT31	physical association	0.720	6
BRD9	physical association	0.560	6
CEP72	physical association	0.560	5
CTNNBL1	physical association	0.560	3
CYSRT1	physical association	0.560	3
DDIT4L	physical association	0.560	3
GOLGA6L9	physical association	0.560	3
HESX1	physical association	0.560	3
KRT40	physical association	0.560	3
KRTAP1-1	physical association	0.560	3
KRTAP10-7	physical association	0.560	3
KRTAP10-9	physical association	0.560	3
MEDAG	physical association	0.560	3
MTUS2	physical association	0.560	3
HNRNPA1L2	physical association	0.400	1
ECE1	physical association	0.370	1

BioGRID (19 interactions; top human partners by supporting records): BRD9 (Two-hybrid; 2 records), KRT31 (Two-hybrid; 2 records), APP (Reconstituted Complex), CEP72 (Two-hybrid), CTNNBL1 (Two-hybrid), DDIT4L (Two-hybrid), GOLGA6L9 (Two-hybrid), HESX1 (Two-hybrid), HNRNPA1L2 (Affinity Capture-MS), KRT40 (Two-hybrid), KRTAP1-1 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), MEDAG (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for CATIP: 56 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	50
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1172755	NM_198559.2(CATIP):c.103T>A (p.Phe35Ile)	Likely pathogenic	criteria provided, single submitter	2

Per-variant reference — Sugi Variant

Explore CATIP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 1,046):

Position(s)	Effect	Δscore	Sites
2:218366570	donor_gain	1.0000
2:218362899	donor_gain	0.9900
2:218364615–218364616	acceptor_gain	0.9900	2
2:218364619	acceptor_gain	0.9900
2:218364622	acceptor_gain	0.9900
2:218364753–218364754	donor_loss	0.9900	6
2:218366550	donor_gain	0.9900
2:218367094	donor_gain	0.9900
2:218367428–218367429	acceptor_loss	0.9900	5
2:218367516	donor_gain	0.9900

AlphaMissense

378 missense substitutions predicted likely pathogenic (of 2,533 scored), across 142 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F351	8	0.840	0.942
F331	7	0.906	0.972
R182	7	0.895	0.982
F196	7	0.887	0.966
W293	7	0.856	0.956
F303	7	0.852	0.962
D251	7	0.839	0.904
F49	7	0.809	0.947
D296	7	0.752	0.824
D330	7	0.746	0.815
G252	6	0.924	0.975
M184	6	0.847	0.925
F346	6	0.816	0.964
H253	6	0.805	0.957
P340	6	0.779	0.855
D200	6	0.769	0.817
F35	5	0.860	0.902
E51	5	0.849	0.934
F171	5	0.841	0.911
G261	5	0.745	0.890

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Renal Papillary Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.97e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	5.74e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	7.01e-05

Disease associations

OMIM: gene MIM:619387 | disease phenotypes: MIM:619379

GenCC curated gene-disease

Mondo (1): spermatogenic failure 54 (MONDO:0023664)

HPO phenotypes

17 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000798	Oligozoospermia
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0012207	Reduced sperm motility
HP:0030974	Cryptozoospermia
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0032562	Tapered sperm head
HP:0033524	Abnormal sperm axoneme morphology

GWAS associations

3 associations:

Study	Trait	p-value
GCST90020028_1079	Hip circumference adjusted for BMI	8e-12
GCST90020028_1080	Hip circumference adjusted for BMI	9e-9
GCST90020028_1077	Hip circumference adjusted for BMI	1e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Ozone	increases oxidation, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Hydroxyl Radical	increases expression, increases oxidation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

12 trials:

NCT	Phase	Status	Title
NCT03414970	Phase 3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	Phase 2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	Phase 2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	Phase 1/2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	Phase 1/2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	Early Phase 1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	Early Phase 1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT07628634	Early Phase 1	RECRUITING	Feasibility Study on the Effect of a Methionine-Reduced Diet on Serum Levels in Pts w/ Solid Tumors
NCT01208974	Not specified	COMPLETED	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery