TFG

trafficking from ER to golgi regulator

Basic information

Region (hg38): 3:100709295-100748964

Links

ENSG00000114354 ∙ NCBI:10342 ∙ OMIM:602498 ∙ HGNC:11758 ∙ Uniprot:Q92734 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary motor and sensory neuropathy, Okinawa type (Supportive), mode of inheritance: AD
• hereditary spastic paraplegia 57 (Supportive), mode of inheritance: AR
• autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation (Supportive), mode of inheritance: AD
• hereditary motor and sensory neuropathy, Okinawa type (Strong), mode of inheritance: AD
• hereditary spastic paraplegia 57 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary motor and sensory, Okinawa type; Spastic paraplegia 57	AR	General	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	Musculoskeletal; Neurologic	17906970; 22883144; 23479643; 23553329; 25098539

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TFG gene.

• Hereditary_motor_and_sensory_neuropathy,_Okinawa_type (345 variants)
• Hereditary_spastic_paraplegia_57 (343 variants)
• not_provided (96 variants)
• Inborn_genetic_diseases (64 variants)
• not_specified (17 variants)
• TFG-related_disorder (11 variants)
• Amyotrophic_Lateral_Sclerosis_with_Sensory_Neuropathy (1 variants)
• Charcot-Marie-Tooth_disease (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TFG gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006070.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	92	2	97
missense	2	3	196	11	1	213
nonsense		1	6			7
start loss						0
frameshift			6			6
splice donor/acceptor (+/-2bp)			1			1
Total	2	4	212	103	3

Highest pathogenic variant AF is 0.0000427838

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TFG	protein_coding	protein_coding	ENST00000240851	7	39606

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.141	0.859	125739	0	8	125747	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	166	222	0.748	0.0000115	2579
Missense in Polyphen		21	41.309	0.50837		530
Synonymous	-1.09	87	75.0	1.16	0.00000372	796
Loss of Function	3.31	6	23.2	0.259	0.00000130	233

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000533	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000336	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules (PubMed:23479643, PubMed:27813252). {ECO:0000269|PubMed:23479643, ECO:0000269|PubMed:27813252}.
• Disease: DISEASE: Neuropathy, hereditary motor and sensory, Okinawa type (HMSNO) [MIM:604484]: A neurodegenerative disorder characterized by young adult onset of proximal muscle weakness and atrophy, muscle cramps, and fasciculations, with later onset of distal sensory impairment. The disorder is slowly progressive and clinically resembles amyotrophic lateral sclerosis. {ECO:0000269|PubMed:22883144, ECO:0000269|PubMed:27813252}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 57, autosomal recessive (SPG57) [MIM:615658]: A complicated form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. {ECO:0000269|PubMed:23479643, ECO:0000269|PubMed:27492651, ECO:0000269|PubMed:27813252}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pathways in cancer - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;EGFR1;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.247

Intolerance Scores

• loftool: 0.391
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.32

Haploinsufficiency Scores

• pHI: 0.154
• hipred: Y
• hipred_score: 0.654
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.859

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tfg

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;positive regulation of I-kappaB kinase/NF-kappaB signaling;COPII vesicle coating
• Cellular component: Golgi membrane;cytoplasm;cytosol;endoplasmic reticulum exit site
• Molecular function: protein binding;identical protein binding