TOGARAM2

Summary

TOGARAM2 (TOG array regulator of axonemal microtubules 2, HGNC:33715) is a protein-coding gene on chromosome 2p23.2, encoding TOG array regulator of axonemal microtubules protein 2 (Q6ZUX3).

Predicted to enable microtubule binding activity. Predicted to be involved in microtubule cytoskeleton organization. Predicted to be located in microtubule cytoskeleton. Predicted to be active in cilium and cytoplasmic microtubule.

Source: NCBI Gene 165186 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 241 total
• MANE Select transcript: NM_199280

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33715
Approved symbol	TOGARAM2
Name	TOG array regulator of axonemal microtubules 2
Location	2p23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43249, LOC165186, Crescerin-2
Ensembl gene	ENSG00000189350
Ensembl biotype	protein_coding
OMIM	620949
Entrez	165186

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000379558, ENST00000401723, ENST00000420297, ENST00000440012, ENST00000460951, ENST00000465300, ENST00000475900, ENST00000864354, ENST00000864355, ENST00000864356, ENST00000929817, ENST00000956354, ENST00000956355

RefSeq mRNA: 3 — MANE Select: NM_199280 NM_001321538, NM_001321539, NM_199280

CCDS: CCDS1769

Canonical transcript exons

ENST00000379558 — 20 exons

Exon	Start	End
ENSE00001553507	28981298	28981538
ENSE00001595895	29014395	29014561
ENSE00001604676	29017154	29017304
ENSE00001611968	29002536	29002747
ENSE00001651769	29011455	29011501
ENSE00001666825	28999181	28999468
ENSE00001705631	28994725	28994862
ENSE00001759600	29003492	29003682
ENSE00001791077	29017792	29017956
ENSE00001798587	28998143	28998253
ENSE00003250024	29051756	29052230
ENSE00003501790	29023086	29023191
ENSE00003521017	29036541	29036757
ENSE00003552197	29022158	29022308
ENSE00003559212	29026853	29027011
ENSE00003610818	29045324	29045410
ENSE00003620829	29035464	29035656
ENSE00003643645	29032934	29033051
ENSE00003650107	29033469	29033563
ENSE00003789548	29024139	29024374

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 99.11.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7900 / max 172.3684, expressed in 200 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19520	0.3042	88
19511	0.1432	60
19521	0.0900	33
19509	0.0827	44
19510	0.0801	39
19522	0.0409	11
19508	0.0290	17
19512	0.0199	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.11	gold quality
bronchial epithelial cell	CL:0002328	98.55	gold quality
bronchus	UBERON:0002185	97.24	gold quality
oocyte	CL:0000023	94.79	gold quality
secondary oocyte	CL:0000655	94.17	gold quality
tibialis anterior	UBERON:0001385	93.64	silver quality
apex of heart	UBERON:0002098	92.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.11	gold quality
granulocyte	CL:0000094	89.39	gold quality
oviduct epithelium	UBERON:0004804	89.31	gold quality
heart right ventricle	UBERON:0002080	88.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.72	gold quality
heart left ventricle	UBERON:0002084	88.23	gold quality
right atrium auricular region	UBERON:0006631	88.11	gold quality
cardiac ventricle	UBERON:0002082	88.07	gold quality
cardiac atrium	UBERON:0002081	87.72	gold quality
gastrocnemius	UBERON:0001388	87.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.61	gold quality
nasal cavity epithelium	UBERON:0005384	87.50	silver quality
fallopian tube	UBERON:0003889	86.68	gold quality
muscle of leg	UBERON:0001383	85.81	gold quality
right lung	UBERON:0002167	84.49	gold quality
caudate nucleus	UBERON:0001873	83.80	gold quality
adenohypophysis	UBERON:0002196	83.70	gold quality
deltoid	UBERON:0001476	83.56	silver quality
hypothalamus	UBERON:0001898	83.40	gold quality
heart	UBERON:0000948	83.39	gold quality
pituitary gland	UBERON:0000007	83.18	gold quality
spleen	UBERON:0002106	82.98	gold quality
nucleus accumbens	UBERON:0001882	82.73	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.93
E-MTAB-7303	no	98.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting TOGARAM2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-665	97.60	65.64	1781

Literature-anchored findings (GeneRIF, showing 1)

• Genetic heterogeneity in hereditary hearing loss: Potential role of kinociliary protein TOGARAM2. (PMID:38374469)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Togaram2	ENSMUSG00000045761
rattus_norvegicus	Togaram2	ENSRNOG00000026344
drosophila_melanogaster	chb	FBGN0021760
caenorhabditis_elegans		WBGENE00000491
caenorhabditis_elegans		WBGENE00000549
caenorhabditis_elegans		WBGENE00013847
caenorhabditis_elegans		WBGENE00015580

Paralogs (3): CLASP1 (ENSG00000074054), CLASP2 (ENSG00000163539), TOGARAM1 (ENSG00000198718)

Protein

Protein identifiers

TOG array regulator of axonemal microtubules protein 2 — Q6ZUX3 (reviewed: Q6ZUX3)

Alternative names: Crescerin-2

All UniProt accessions (4): B5MCN5, C9JJW1, C9JLI7, Q6ZUX3

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the Crescerin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZUX3-1	1	yes
Q6ZUX3-2	2
Q6ZUX3-3	3

RefSeq proteins (3): NP_001308467, NP_001308468, NP_954974* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR024395	CLASP_N_dom	Domain
IPR034085	TOG	Domain

Pfam: PF12348

UniProt features (20 total): sequence variant 8, splice variant 5, region of interest 4, chain 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZUX3-F1	61.60	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, IRF1_Q6, HFH1_01, FREAC7_01, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM, GOMF_CYTOSKELETAL_PROTEIN_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, JOHNSTONE_PARVB_TARGETS_3_UP, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, FORTSCHEGGER_PHF8_TARGETS_DN, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOCC_SUPRAMOLECULAR_POLYMER

GO Biological Process (3): microtubule cytoskeleton organization (GO:0000226), negative regulation of cytoskeleton organization (GO:0051494), negative regulation of supramolecular fiber organization (GO:1902904)

GO Molecular Function (1): microtubule binding (GO:0008017)

GO Cellular Component (3): cytoplasmic microtubule (GO:0005881), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton organization	2
microtubule-based process	1
negative regulation of organelle organization	1
regulation of cytoskeleton organization	1
negative regulation of cellular component organization	1
supramolecular fiber organization	1
regulation of supramolecular fiber organization	1
tubulin binding	1
cytoplasm	1
microtubule	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1

Protein interactions and networks

STRING

500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOGARAM2	GARIN1A	Q6NXP2	471
TOGARAM2	NUTM2D	Q5VT03	448
TOGARAM2	COL25A1	Q9BXS0	447
TOGARAM2	OR51A4	Q8NGJ6	420
TOGARAM2	SHISAL2A	Q6UWV7	403
TOGARAM2	OBI1	Q5W0B1	400
TOGARAM2	ZNF716	A6NP11	397
TOGARAM2	BTBD17	A6NE02	372
TOGARAM2	TSPYL6	Q8N831	371
TOGARAM2	FAM25A	B3EWG3	370
TOGARAM2	OVCH1	Q7RTY7	367
TOGARAM2	B3GNT9	Q6UX72	367
TOGARAM2	Q8WV35	Q8WV35	356
TOGARAM2	FBXO36	Q8NEA4	348
TOGARAM2	CLIP4	Q8N3C7	348

IntAct

2 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (3): FAM179A (Affinity Capture-MS), FAM179A (Protein-peptide), FAM179A (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A494C1R9, A2AKB4, A2APT9, A6NKD2, A8MT33, B0BN44, E9PGG2, F5GYI3, O19110, O88852, P0CV98, P0CV99, P0CW00, P0CW01, Q01534, Q03386, Q0P5N2, Q12967, Q14684, Q2M329, Q3U3N0, Q5F267, Q5I0E2, Q5R5G8, Q5R866, Q5SYB0, Q5VTJ3, Q60953, Q69ZB3, Q6ZUX3, Q7TQI8, Q80VJ8, Q80VR2, Q86VY4, Q8BSI6, Q8IZJ4, Q8N831, Q8VD63, Q95LS7, Q96FG2

Diamond homologs: Q3TYG6, Q6A070, Q6ZUX3, Q9Y4F4, Q8RWY6, Q17423

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	195
Likely benign	26
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4702 predictions. Top by Δscore:

Variant	Effect	Δscore
2:28994717:A:AG	acceptor_gain	1.0000
2:28994718:C:G	acceptor_gain	1.0000
2:28994720:CTTA:C	acceptor_loss	1.0000
2:28994722:TA:T	acceptor_loss	1.0000
2:28994723:A:AG	acceptor_gain	1.0000
2:28994723:A:AT	acceptor_loss	1.0000
2:28994724:G:A	acceptor_loss	1.0000
2:28994724:G:GG	acceptor_gain	1.0000
2:28994860:AAGGT:A	donor_loss	1.0000
2:28994861:AGGTA:A	donor_loss	1.0000
2:28994863:GTAA:G	donor_loss	1.0000
2:28994864:T:A	donor_loss	1.0000
2:28998134:T:TA	acceptor_gain	1.0000
2:28998141:A:AG	acceptor_gain	1.0000
2:28998142:G:GA	acceptor_gain	1.0000
2:29017152:A:AG	acceptor_gain	1.0000
2:29017153:G:GG	acceptor_gain	1.0000
2:29017300:GGAAG:G	donor_gain	1.0000
2:29017301:G:GT	donor_gain	1.0000
2:29017302:A:T	donor_gain	1.0000
2:29024312:GGC:G	donor_gain	1.0000
2:29024313:GC:G	donor_gain	1.0000
2:29024350:T:TA	donor_gain	1.0000
2:29024351:G:GA	donor_gain	1.0000
2:29024375:G:GG	donor_gain	1.0000
2:29026847:TTTCA:T	acceptor_loss	1.0000
2:29026848:TTCAG:T	acceptor_loss	1.0000
2:29026849:TCA:T	acceptor_loss	1.0000
2:29026850:CAGC:C	acceptor_loss	1.0000
2:29026851:A:AG	acceptor_gain	1.0000

AlphaMissense

6571 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:29032942:G:A	G674D	0.987
2:29024194:T:C	L558P	0.982
2:29051821:T:A	W930R	0.977
2:29051821:T:C	W930R	0.977
2:29024173:C:A	A551D	0.975
2:29024280:T:C	F587L	0.972
2:29024282:C:A	F587L	0.972
2:29024282:C:G	F587L	0.972
2:29026992:G:C	D665H	0.971
2:29032980:T:C	F687L	0.971
2:29032982:T:A	F687L	0.971
2:29032982:T:G	F687L	0.971
2:29026884:G:C	A629P	0.970
2:29035591:G:C	G785R	0.968
2:29032945:G:C	R675P	0.967
2:29026894:T:C	L632P	0.966
2:29036598:G:C	A826P	0.965
2:29036689:T:C	L856P	0.965
2:29036554:T:C	F811S	0.964
2:29036602:T:C	L827P	0.964
2:29024196:T:C	F559L	0.963
2:29024198:C:A	F559L	0.963
2:29024198:C:G	F559L	0.963
2:29051807:T:A	V925D	0.963
2:29023086:G:C	W504C	0.962
2:29023086:G:T	W504C	0.962
2:29032941:G:C	G674R	0.962
2:29036571:G:C	D817H	0.962
2:29051912:T:A	L960H	0.962
2:29051912:T:C	L960P	0.962

dbSNP variants (sampled 300 via entrez): RS1000060434 (2:29047990 T>A), RS1000077322 (2:28955378 G>A), RS1000109408 (2:29025309 G>A,C), RS1000168627 (2:29021311 C>T), RS1000171842 (2:28989769 A>G), RS1000187873 (2:28982638 C>T), RS1000234487 (2:28957371 G>A), RS1000266462 (2:29016151 G>C), RS1000267961 (2:29048398 G>A), RS1000269016 (2:28978629 G>C,T), RS1000280147 (2:28978897 T>G), RS1000323292 (2:29015256 A>G), RS1000335556 (2:29001011 T>C), RS1000366553 (2:29000752 C>A), RS1000376124 (2:29005203 G>A,C)

Disease associations

OMIM: gene MIM:620949 | disease phenotypes: MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Limited	Autosomal recessive

Mondo (2): hearing loss, autosomal recessive (MONDO:0019588), nonsyndromic genetic hearing loss (MONDO:0019497)

Orphanet (2): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000578_4	Major depressive disorder	2.000000e-06
GCST002309_1	Diastolic blood pressure (alcohol consumption interaction)	7.000000e-08
GCST004068_63	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	6.000000e-06
GCST007317_9	Response to ketamine in bipolar disorder or major depression (dissociation effects)	7.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0009748	response to ketamine
EFO:0009750	dissociation measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564609	Deafness, Autosomal Recessive (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
entinostat	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	decreases methylation	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Zinc	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations