HOATZ

Summary

HOATZ (HOATZ cilia and flagella associated protein, HGNC:25061) is a protein-coding gene on chromosome 11q23.1, encoding Cilia- and flagella-associated protein HOATZ (Q6PI97). Required for motile ciliogenesis and flagellar genesis by mediating the maturation of the glycolytic enzyme ENO4.

Predicted to be involved in axoneme assembly; flagellated sperm motility; and spermatogenesis. Predicted to be located in cilium and cytoplasm.

Source: NCBI Gene 399949 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 6 total — 1 pathogenic
• MANE Select transcript: NM_001100388

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25061
Approved symbol	HOATZ
Name	HOATZ cilia and flagella associated protein
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46266
Ensembl gene	ENSG00000183644
Ensembl biotype	protein_coding
Entrez	399949

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000332814, ENST00000375618, ENST00000529167, ENST00000529661, ENST00000971263

RefSeq mRNA: 2 — MANE Select: NM_001100388 NM_001100388, NM_207430

CCDS: CCDS41712, CCDS41713

Canonical transcript exons

ENST00000375618 — 6 exons

Exon	Start	End
ENSE00001363935	111515511	111515552
ENSE00001368852	111516040	111516110
ENSE00002168144	111536770	111537043
ENSE00003488737	111533746	111533805
ENSE00003658532	111534412	111534464
ENSE00003921254	111514778	111515010

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 98.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8081 / max 325.1232, expressed in 109 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116618	0.4994	88
116620	0.1312	38
116619	0.1035	30
116617	0.0259	6
116624	0.0194	4
116622	0.0129	8
116621	0.0083	5
116623	0.0074	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.99	gold quality
bronchial epithelial cell	CL:0002328	98.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.50	gold quality
bronchus	UBERON:0002185	97.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.84	gold quality
left testis	UBERON:0004533	86.94	gold quality
right testis	UBERON:0004534	85.85	gold quality
fallopian tube	UBERON:0003889	85.84	gold quality
testis	UBERON:0000473	83.72	gold quality
oviduct epithelium	UBERON:0004804	82.57	gold quality
right lung	UBERON:0002167	82.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.42	gold quality
epithelium of nasopharynx	UBERON:0001951	76.64	gold quality
sperm	CL:0000019	75.74	silver quality
nasal cavity mucosa	UBERON:0001826	74.45	gold quality
left uterine tube	UBERON:0001303	72.86	gold quality
caput epididymis	UBERON:0004358	71.84	gold quality
hypothalamus	UBERON:0001898	67.15	gold quality
nasal cavity epithelium	UBERON:0005384	66.96	silver quality
endometrium	UBERON:0001295	65.85	gold quality
endocervix	UBERON:0000458	65.76	gold quality
upper lobe of left lung	UBERON:0008952	63.97	gold quality
upper lobe of lung	UBERON:0008948	62.99	gold quality
caudate nucleus	UBERON:0001873	62.50	gold quality
lung	UBERON:0002048	62.46	gold quality
corpus callosum	UBERON:0002336	60.23	gold quality
trachea	UBERON:0003126	58.54	gold quality
amygdala	UBERON:0001876	58.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.06	gold quality
Ammon’s horn	UBERON:0001954	57.46	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	1455.86
E-CURD-114	yes	63.05
E-HCAD-1	yes	31.54
E-MTAB-10287	yes	27.55
E-GEOD-130148	yes	17.64
E-MTAB-9388	yes	7.48
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting HOATZ, 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-6844	99.82	70.69	2423
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-934	98.49	70.44	581
HSA-MIR-3680-5P	98.06	66.20	394
HSA-MIR-744-3P	97.99	67.76	637
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-596	97.48	63.13	469
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-4695-3P	96.71	67.21	836
HSA-MIR-582-3P	96.69	67.38	1019
HSA-MIR-125B-2-3P	96.69	68.38	1210

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hoatz	ENSMUSG00000032057
rattus_norvegicus	Hoatz	ENSRNOG00000043383

Paralogs (2): SELENON (ENSG00000162430), BEND2 (ENSG00000177324)

Protein

Protein identifiers

Cilia- and flagella-associated protein HOATZ — Q6PI97 (reviewed: Q6PI97)

All UniProt accessions (3): E9PN74, Q6PI97, H0YE60

UniProt curated annotations — full annotation on UniProt →

Function. Required for motile ciliogenesis and flagellar genesis by mediating the maturation of the glycolytic enzyme ENO4.

Subcellular location. Cytoplasm. Cell projection. Cilium.

Similarity. Belongs to the HOATZ family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6PI97-1	1	yes
Q6PI97-2	2
Q6PI97-3	3

RefSeq proteins (2): NP_001093858, NP_997313 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040681	HOATZ-like	Family

Pfam: PF17664

UniProt features (7 total): region of interest 3, splice variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PI97-F1	74.34	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): AREB6_01, GOBP_MALE_GAMETE_GENERATION, CEBP_Q2, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, OCT1_07, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, AFP1_Q6, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_CELL_PROJECTION_ORGANIZATION, AML1_01, HNF1_01

GO Biological Process (4): spermatogenesis (GO:0007283), flagellated sperm motility (GO:0030317), axoneme assembly (GO:0035082), cilium assembly (GO:0060271)

GO Molecular Function (0):

GO Cellular Component (3): cytoplasm (GO:0005737), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOATZ	ANKRD66	B4E2M5	540
HOATZ	ANKUB1	A6NFN9	468
HOATZ	PRR33	A8MZF0	433
HOATZ	CFAP126	Q5VTH2	431
HOATZ	C11orf87	Q6NUJ2	430
HOATZ	LMNTD2	Q8IXW0	427
HOATZ	LRRC71	Q8N4P6	414
HOATZ	SNRNP27	Q8WVK2	400
HOATZ	MAP3K19	Q56UN5	395
HOATZ	FAM216B	Q8N7L0	392
HOATZ	RSRC1	Q96IZ7	363
HOATZ	POU2AF2	Q8IXP5	348
HOATZ	ENO4	A6NNW6	337
HOATZ	NWD2	Q9ULI1	333
HOATZ	DYNLT5	Q8N7M0	327

IntAct

0 interactions, top by confidence:

BioGRID (2): C11orf88 (Co-fractionation), C11orf88 (Co-fractionation)

ESM2 similar proteins: A0A1B0GVG6, G3UW99, O08664, O55777, P05909, P0C1K0, P12453, P16903, P20880, P24097, P24109, Q1KN10, Q1KN12, Q1KN14, Q1KN16, Q1KN19, Q1KN21, Q1L9C7, Q1RMQ5, Q1X6X9, Q1X6Y1, Q1X6Y4, Q1X6Y6, Q1X6Z2, Q1X6Z3, Q1X6Z4, Q2TBV0, Q3KP22, Q4VKV6, Q5J2D6, Q5ZM46, Q63630, Q68D20, Q6PI97, Q6W0C5, Q80VY2, Q82855, Q86YL5, Q873B8, Q8C1R3

Diamond homologs: A5PN52, B6LI37, Q32P68, Q6PI97, Q80Y73

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
831566	NC_000011.9:g.(?111171709)(111965694_?)del	Pathogenic

SpliceAI

688 predictions. Top by Δscore:

Variant	Effect	Δscore
11:111515006:GTCTG:G	donor_gain	1.0000
11:111515007:TCTGG:T	donor_loss	1.0000
11:111515008:CTGGT:C	donor_loss	1.0000
11:111515009:TGGTG:T	donor_loss	1.0000
11:111515010:GGTG:G	donor_loss	1.0000
11:111515011:G:GG	donor_gain	1.0000
11:111515012:T:G	donor_loss	1.0000
11:111515013:G:GT	donor_loss	1.0000
11:111515014:AG:A	donor_loss	1.0000
11:111515553:G:GG	donor_gain	1.0000
11:111516038:A:AG	acceptor_gain	1.0000
11:111516039:G:GG	acceptor_gain	1.0000
11:111514994:G:GT	donor_gain	0.9900
11:111515508:TAGA:T	acceptor_loss	0.9900
11:111515509:A:AG	acceptor_gain	0.9900
11:111515509:A:C	acceptor_loss	0.9900
11:111515510:G:GA	acceptor_loss	0.9900
11:111515510:G:GG	acceptor_gain	0.9900
11:111515548:TAACA:T	donor_gain	0.9900
11:111515551:CA:C	donor_gain	0.9900
11:111515552:AG:A	donor_loss	0.9900
11:111515553:GTA:G	donor_loss	0.9900
11:111515554:TAAGT:T	donor_loss	0.9900
11:111515555:AA:A	donor_loss	0.9900
11:111515556:AGTA:A	donor_loss	0.9900
11:111533818:G:GG	donor_gain	0.9900
11:111534410:A:AG	acceptor_gain	0.9900
11:111534411:G:GG	acceptor_gain	0.9900
11:111534411:GAAA:G	acceptor_gain	0.9900
11:111515510:GA:G	acceptor_gain	0.9800

AlphaMissense

1104 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:111533790:A:C	R128S	0.991
11:111533790:A:T	R128S	0.991
11:111514860:T:C	F26L	0.986
11:111514862:T:A	F26L	0.986
11:111514862:T:G	F26L	0.986
11:111533777:T:C	L124S	0.985
11:111533799:G:C	R131S	0.985
11:111533799:G:T	R131S	0.985
11:111514905:T:A	W41R	0.984
11:111514905:T:C	W41R	0.984
11:111533746:G:C	A114P	0.982
11:111533774:T:C	L123P	0.982
11:111514894:C:A	A37D	0.979
11:111533757:A:C	R117S	0.979
11:111533757:A:T	R117S	0.979
11:111514903:T:C	F40S	0.972
11:111514861:T:C	F26S	0.967
11:111534414:A:C	K134N	0.960
11:111534414:A:T	K134N	0.960
11:111533786:A:C	Q127P	0.959
11:111533789:G:C	R128T	0.959
11:111514902:T:C	F40L	0.958
11:111514904:C:A	F40L	0.958
11:111514904:C:G	F40L	0.958
11:111514907:G:C	W41C	0.953
11:111514907:G:T	W41C	0.953
11:111533789:G:T	R128I	0.953
11:111533798:G:C	R131T	0.950
11:111533756:G:T	R117I	0.946
11:111514861:T:G	F26C	0.944

dbSNP variants (sampled 300 via entrez): RS1000235785 (11:111518010 T>C), RS1000435883 (11:111518384 T>C), RS1000570043 (11:111516302 A>G), RS1000769142 (11:111516584 G>C,T), RS1001039203 (11:111530494 T>C), RS1001090155 (11:111530820 C>T), RS1001372741 (11:111531101 T>C), RS1001384685 (11:111517704 C>A), RS1001573107 (11:111524566 A>G), RS1001643921 (11:111531984 C>T), RS1001857668 (11:111522730 G>A), RS1001928556 (11:111530018 C>A,G), RS1001988465 (11:111531710 A>G), RS1002129365 (11:111523312 T>C), RS1002371664 (11:111516714 CT>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:168000, MIM:171300, MIM:606864, MIM:615106

GenCC curated gene-disease

Mondo (4): pheochromocytoma/paraganglioma syndrome 1 (MONDO:0008192), pheochromocytoma (MONDO:0008233), Carney-Stratakis syndrome (MONDO:0011740), Cowden syndrome 3 (MONDO:0014045)

Orphanet (3): Cowden syndrome (Orphanet:201), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Carney-Stratakis syndrome (Orphanet:97286)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007563_14	Allergic disease (asthma, hay fever or eczema)	1.000000e-10
GCST007564_5	Asthma or allergic disease (pleiotropy)	6.000000e-11
GCST008103_146	Bipolar disorder	3.000000e-06
GCST010703_266	Brain morphology (MOSTest)	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D010673	Pheochromocytoma	C04.557.465.625.650.700.725; C04.557.580.625.650.700.725
C564650	Carney-Stratakis Syndrome (supp.)

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
ethyl-p-hydroxybenzoate	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01379898	PHASE4	COMPLETED	Phenoxybenzamine Versus Doxazosin in PCC Patients
NCT01959711	PHASE4	COMPLETED	Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy
NCT05702944	PHASE4	RECRUITING	The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00126412	PHASE3	COMPLETED	Meta-Iodobenzylguanidine (123I mIBG) Scintigraphy in Patients Being Evaluated for Phaeochromocytoma or Neuroblastoma
NCT01373736	PHASE3	UNKNOWN	123I-MIBG Scintigraphy in Patients Being Evaluated for Neuroendocrine Tumors
NCT03176693	PHASE3	COMPLETED	Preoperative Alpha Blockade for Pheochromocytoma
NCT00002608	PHASE2	COMPLETED	Combination Chemotherapy and Tamoxifen in Treating Patients With Solid Tumors
NCT00028106	PHASE2	COMPLETED	131MIBG to Treat Malignant Pheochromocytoma
NCT00107289	PHASE2	RECRUITING	Iodine I 131 Metaiodobenzylguanidine in Treating Patients With Recurrent, Progressive, or Refractory Neuroblastoma or Malignant Pheochromocytoma or Paraganglioma
NCT00466856	PHASE2	TERMINATED	Internal Radiation Therapy in Treating Patients With Liver Metastases From Neuroendocrine Tumors
NCT00843037	PHASE2	COMPLETED	Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma
NCT00874614	PHASE2	UNKNOWN	A Study Evaluating Ultratrace Iobenguane I131 in Patients With Malignant Relapsed/Refractory Pheochromocytoma/Paraganglioma
NCT00923481	PHASE2	COMPLETED	A Broad Multi-histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) in Advanced Colorectal, Non-small Cell Lung, Head and Neck Hepatocellular and Renal Cell Carcinomas, and Pheochromocytoma and Thyroid Tumors (Multi-H…
NCT01152827	PHASE2	COMPLETED	RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid
NCT01413503	PHASE2	COMPLETED	A Phase II Study of 131I- Metaiodobenzylguanidine (MIBG) for Treatment of Metastatic or Unresectable Pheochromocytoma and Related Tumors
NCT01635907	PHASE2	COMPLETED	Dovitinib in Neuroendocrine Tumors
NCT01967576	PHASE2	COMPLETED	Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma
NCT03165721	PHASE2	TERMINATED	A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer
NCT03206060	PHASE2	RECRUITING	Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma
NCT03839498	PHASE2	ACTIVE_NOT_RECRUITING	Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Pheochromocytoma/Paraganglioma
NCT03946527	PHASE2	ACTIVE_NOT_RECRUITING	LAnreotide in Metastatic Pheochromocytoma / PARAganglioma (LAMPARA)
NCT04276597	PHASE2	WITHDRAWN	Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET.
NCT04320589	PHASE2	COMPLETED	the Effect of Dexmedetomidine and Magnesium Sulfate in Open Resection of Pheochromocytoma
NCT04400474	PHASE2	COMPLETED	Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study
NCT04711135	PHASE2	ACTIVE_NOT_RECRUITING	Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs
NCT04924075	PHASE2	RECRUITING	Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
NCT05133349	PHASE2	UNKNOWN	A Prospective Phase II Efficacy and Safety Study of Anlotinib in Metastatic or Locally Advanced Pheochromocytoma/ Paraganglioma : Open-label Single-arm, Exploratory Trial
NCT05883085	PHASE2	UNKNOWN	A Study on the Safety and Effectiveness of Anlotinib for Neoadjuvant Treatment of PPGL
NCT05885386	PHASE2	UNKNOWN	A Study on the Safety and Effectiveness of Temozolomide for Neoadjuvant Treatment of PPGL
NCT06045260	PHASE2	RECRUITING	Receptor Radionuclide Therapy With 177Lu-DOTATOC
NCT06233903	PHASE2	WITHDRAWN	18F-mFBG Expression in Neural Crest Tumors and Organs Innervated by the Sympathetic Nervous System
NCT06429397	PHASE2	NOT_YET_RECRUITING	Anlotinib Combined With Benmelstobart for Advanced Pheochromocytoma
NCT06503146	PHASE2	RECRUITING	18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection
NCT06683846	PHASE2	RECRUITING	Ivonescimab in the Treatment of Multiple Advanced Tumors
NCT07167329	PHASE2	RECRUITING	Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial
NCT00002947	PHASE1	TERMINATED	Indium In 111 Pentetreotide in Treating Patients With Refractory Cancer
NCT00004847	PHASE1	RECRUITING	Diagnosis of Pheochromocytoma
NCT00049023	PHASE1	COMPLETED	Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors