TRAPPC9

trafficking protein particle complex subunit 9, the group of Trafficking protein particle complex subunits

Basic information

Region (hg38): 8:139727725-140458579

Links

ENSG00000167632 ∙ NCBI:83696 ∙ OMIM:611966 ∙ HGNC:30832 ∙ Uniprot:Q96Q05 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 13 (Definitive), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 13 (Moderate), mode of inheritance: AR
• intellectual disability, autosomal recessive 13 (Strong), mode of inheritance: AR
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 13	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	Craniofacial; Endocrine; Neurologic	17120046; 20004765; 20004763; 20004764; 21629298; 22549410; 22989526

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAPPC9 gene.

• not provided (25 variants)
• Intellectual disability, autosomal recessive 13 (15 variants)
• Abnormality of the nervous system (2 variants)
• Inborn genetic diseases (2 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAPPC9 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	186	9	200
missense		1	269	7		277
nonsense	14	6	1			21
start loss						0
frameshift	16	6	1			23
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	10	1			13
splice region			11	20	2	33
non coding	5	1	34	128	51	219
Total	37	24	312	321	60

Highest pathogenic variant AF is 0.0000263

Variants in TRAPPC9

This is a list of pathogenic ClinVar variants found in the TRAPPC9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-139730384-A-G		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
8-139730485-C-T		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
8-139730529-C-T		Intellectual Disability, Recessive	Conflicting classifications of pathogenicity (Jul 01, 2023)
8-139730686-G-A		Intellectual Disability, Recessive	Likely benign (Jun 14, 2016)
8-139730730-G-A		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
8-139730776-T-G		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
8-139730880-C-T		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
8-139730896-C-G			Likely benign (Jul 15, 2018)
8-139730957-G-A		Intellectual Disability, Recessive	Benign (Jul 09, 2018)
8-139730981-C-G		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
8-139730996-G-C		Intellectual Disability, Recessive	Uncertain significance (Jun 14, 2016)
8-139731065-G-T		not specified	Uncertain significance (May 03, 2024)
8-139731070-C-T		Inborn genetic diseases	Likely benign (Jan 22, 2024)
8-139731071-G-A			Uncertain significance (Oct 07, 2021)
8-139731072-C-G			Uncertain significance (Mar 26, 2022)
8-139731087-C-T		not specified • Inborn genetic diseases • TRAPPC9-related disorder	Conflicting classifications of pathogenicity (Jan 25, 2024)
8-139731088-G-A		Inborn genetic diseases	Likely benign (Oct 03, 2023)
8-139731094-A-C		Intellectual Disability, Recessive • not specified • Intellectual disability • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 22, 2024)
8-139731097-G-T		Intellectual Disability, Recessive • not specified • Inborn genetic diseases • TRAPPC9-related disorder	Conflicting classifications of pathogenicity (Jan 20, 2024)
8-139731103-G-T			Uncertain significance (Mar 18, 2022)
8-139731108-A-T			Uncertain significance (Nov 15, 2021)
8-139731118-T-G		not specified • Inborn genetic diseases	Benign/Likely benign (Jan 24, 2024)
8-139731122-A-G		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
8-139731144-C-T		not specified • Intellectual disability, autosomal recessive 13	Uncertain significance (Jul 06, 2021)
8-139731145-G-A			Likely benign (Sep 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAPPC9	protein_coding	protein_coding	ENST00000389328	23	726093

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.29e-14	1.00	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	626	739	0.847	0.0000489	8073
Missense in Polyphen		331	398.34	0.83096		4318
Synonymous	-1.64	353	316	1.12	0.0000231	2503
Loss of Function	3.23	32	58.7	0.545	0.00000318	650

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00144	0.00142
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000276	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000382	0.000378
Middle Eastern	0.000276	0.000272
South Asian	0.000196	0.000196
Other	0.000672	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex. May function in neuronal cells differentiation. May play a role in vesicular transport from endoplasmic reticulum to Golgi. {ECO:0000269|PubMed:15951441}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Intolerance Scores

• loftool: 0.0201
• rvis_EVS: -1.65
• rvis_percentile_EVS: 2.77

Haploinsufficiency Scores

• pHI: 0.167
• hipred: Y
• hipred_score: 0.526
• ghis: 0.610

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.380

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trappc9
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype

Gene ontology

• Biological process: cerebral cortex development;neuron differentiation;COPII vesicle coating;positive regulation of NF-kappaB transcription factor activity
• Cellular component: Golgi membrane;endoplasmic reticulum;trans-Golgi network;cytosol;TRAPP complex
• Molecular function: protein binding;Rab guanyl-nucleotide exchange factor activity