TOGARAM1

protein-coding

TOG array regulator of axonemal microtubules 1, the group of TOG domain containing

Gene summary

Predicted to enable microtubule binding activity. Involved in cilium assembly. Located in axoneme. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA0423
FAM179B

MANE transcript

NM_001308120.2

Inheritance

ClinVar variants

P:22U:249B:35

Top phenotype

Joubert syndrome 37

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr14:44,962,190-45,074,431

External References & Databases

Ensembl (ENSG00000198718)

Transcript & Mutation Effects

hg38 • Region Span ~112.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ciliopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: G2P

ciliopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: Franklin by Genoox

A trio-based whole exome sequencing (WES) strategy was used to identify candidate variants in the TOGARAM1 gene. In silico, in vitro and in vivo (Caenorhabditis elegans) studies were carried out to explore the impact of mutations on protein structure and function, and relevant biological processes. Results TOGARAM1 encodes a member of the Crescerin1 family of proteins regulating microtubule dynamics. Its orthologue in C. elegans, che-12, is expressed in a subset of sensory neurons and localises in the dendritic cilium where it is required for chemosensation. Nematode lines harbouring the corresponding missense variant in TOGARAM1 were generated by CRISPR/Cas9 technology. Although chemotaxis ability on a NaCl gradient was not affected, che-12 point mutants displayed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. Finally, in vitro analysis of microtubule polymerisation in the presence of wild-type or mutant TOG2 domain revealed a faster polymerisation associated with the mutant protein, suggesting aberrant tubulin binding.

Joubert syndrome 37STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030933

Submitter: PanelApp Australia

Joubert syndrome 37STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030933

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Joubert syndrome 37AR

Manifestation: Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial

Refs: 32453716; 32747439

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TOGARAM1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 243

not providedTotal: 49

Joubert syndrome 37Total: 24

Joubert syndromeTotal: 7

Brown syndromeTotal: 2

CiliopathyTotal: 1

TOGARAM1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001308120.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				29 clinvar	1 clinvar	30
missense	2 clinvar	2 clinvar	246 clinvar	5 clinvar		255
nonsense	3 clinvar	4 clinvar				7
start loss						0
frameshift	1 clinvar	8 clinvar	2 clinvar			11
splice donor/acceptor (+/-2bp)		2 clinvar	1 clinvar			3
Total	6	16	249	34	1	306

Highest pathogenic variant AF is 0.00005452326

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001308120.2	RefSeq	NP_001295049.1	20	MANE Select
ENST00000361462.7	Ensembl	ENSP00000354917.2	20	MANE Select
NM_015091.4	RefSeq	NP_055906.2	19	Standard
ENST00000361577.7	Ensembl	ENSP00000355045.3	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of microtubule polymerization
axoneme assembly
non-motile cilium assembly

Cellular Component

cytoplasm
microtubule
cilium
ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361577
Coding exons: 19
Length: 112224
Individuals with no LoFs: 125652
Homozygous LoFs: 0
Heterozygous LoFs: 96
Defined: 125748
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.607	835	886	0.943	0.0000426	11140
Missense (PolyPhen)		232	277	0.83755		3559
Synonymous	0.632	314	329	0.956	0.0000157	3501
Loss of Function	4.92	27	72.1	0.374	0.00000401	913

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00033	0.00032	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00042	0.00041	rare
South Asian	0.00046	0.00046	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for normal structure and function of primary cilia. Plays a role in the organization of axoneme microtubule bundles in primary cilia (By similarity). Interacts with microtubules and promotes microtubule polymerization via its HEAT repeat domains, especially those in TOG region 2 and 4 (By similarity). {ECO:0000250|UniProtKB:Q17423, ECO:0000250|UniProtKB:Q6A070}.;

Recessive Scores

pRec: 0.0961

Intolerance Scores

RVIS EVS: -1.1
RVIS percentile EVS: 6.97

Essentials

Essential (gene trap): N