LITAF

lipopolysaccharide induced TNF factor

Basic information

Region (hg38): 16:11546875-11636381

Links

ENSG00000189067

∙ NCBI:9516 ∙ OMIM:603795 ∙ HGNC:16841 ∙ Uniprot:Q99732 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Charcot-Marie-Tooth disease type 1C (Strong), mode of inheritance: AD
Charcot-Marie-Tooth disease type 1C (Supportive), mode of inheritance: AD
Charcot-Marie-Tooth disease (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, type 1C	AD	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	Neurologic	11713717; 12525712; 19541485; 20301384; 23319192

ClinVar

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

Charcot-Marie-Tooth_disease_type_1C (173 variants)
not_provided (66 variants)
Inborn_genetic_diseases (42 variants)
Charcot-Marie-Tooth_disease (30 variants)
not_specified (15 variants)
LITAF-related_disorder (4 variants)
Charcot-Marie-Tooth_disease,_type_I (3 variants)
Distal_spinal_muscular_atrophy (1 variants)
Tip-toe_gait (1 variants)
Hereditary_ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LITAF gene is commonly pathogenic or not. These statistics are base on transcript: NM_001136472.2. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	42 clinvar	1 clinvar	45
missense	5 clinvar	4 clinvar	99 clinvar	15 clinvar	2 clinvar	125
nonsense			1 clinvar			1
start loss			2			2
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)						0
Total	5	4	108	57	3

Highest pathogenic variant AF is 0.000008892793

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LITAF	protein_coding	protein_coding	ENST00000571688	3	88385

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0308	0.823	125734	0	4	125738	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.224	97	103	0.938	0.00000635	1029
Missense in Polyphen		21	31.116	0.67489		342
Synonymous	-0.175	48	46.5	1.03	0.00000333	342
Loss of Function	1.13	3	5.99	0.501	2.54e-7	68

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000879
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation (PubMed:23166352). Plays a role in targeting endocytosed EGFR and ERGG3 for lysosomal degradation, and thereby helps downregulate downstream signaling cascades (PubMed:23166352). Helps recruit the ESCRT complex components TSG101, HGS and STAM to cytoplasmic membranes (PubMed:23166352). Probably plays a role in regulating protein degradation via its interaction with NEDD4 (PubMed:15776429). May also contribute to the regulation of gene expression in the nucleus (PubMed:10200294, PubMed:15793005). Binds DNA (in vitro) and may play a synergistic role with STAT6 in the nucleus in regulating the expression of various cytokines (PubMed:15793005). May regulate the expression of numerous cytokines, such as TNF, CCL2, CCL5, CXCL1, IL1A and IL10 (PubMed:10200294, PubMed:15793005). {ECO:0000269|PubMed:15793005, ECO:0000269|PubMed:23166352, ECO:0000303|PubMed:15776429, ECO:0000305|PubMed:10200294}.;
Disease: DISEASE: Charcot-Marie-Tooth disease 1C (CMT1C) [MIM:601098]: A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. {ECO:0000269|PubMed:12525712, ECO:0000269|PubMed:15776429, ECO:0000269|PubMed:15786462, ECO:0000269|PubMed:16118794, ECO:0000269|PubMed:21896645, ECO:0000269|PubMed:23166352, ECO:0000269|PubMed:24604904}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in LITAF may be involved in extramammary Paget disease (EMPD) carcinogenesis. EMPD is a cancerous disease representing about 8% of all malignant skin cancers; it usually appears in the anogenital area and can be fatal by metastasizing to internal organs when left untreated for a long time. The clinical features are usually those of eczematous eruptions with weeping and crust formation. {ECO:0000269|PubMed:15197774}.;
Pathway: Lysosome - Homo sapiens (human) (Consensus)

Recessive Scores

pRec: 0.207

Intolerance Scores

loftool: 0.0585
rvis_EVS: -0.05
rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

pHI: 0.253
hipred: Y
hipred_score: 0.583
ghis: 0.508

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.212

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Litaf
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; immune 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); hematopoietic system phenotype;

Gene ontology

Biological process: regulation of cytokine production;regulation of transcription by RNA polymerase II;aging;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of transcription by RNA polymerase II;cellular response to lipopolysaccharide;negative regulation of NIK/NF-kappaB signaling
Cellular component: Golgi membrane;nucleoplasm;lysosomal membrane;Golgi apparatus;cytosol;plasma membrane;cytoplasmic side of plasma membrane;intracellular membrane-bounded organelle;cytoplasmic side of early endosome membrane;cytoplasmic side of late endosome membrane;cytoplasmic side of lysosomal membrane
Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;zinc ion binding;WW domain binding