IGHMBP2

immunoglobulin mu DNA binding protein 2, the group of UPF1 like RNA helicases|Zinc fingers AN1-type

Basic information

Region (hg38): 11:68903862-68940602

Links

ENSG00000132740 ∙ NCBI:3508 ∙ OMIM:600502 ∙ HGNC:5542 ∙ Uniprot:P38935 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive distal spinal muscular atrophy 1 (Definitive), mode of inheritance: AR
• autosomal recessive distal spinal muscular atrophy 1 (Strong), mode of inheritance: AR
• autosomal recessive distal spinal muscular atrophy 1 (Definitive), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2S (Strong), mode of inheritance: AR
• autosomal recessive distal spinal muscular atrophy 1 (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2S (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2S (Definitive), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2S (Strong), mode of inheritance: AR
• autosomal recessive distal spinal muscular atrophy 1 (Strong), mode of inheritance: AR
• hereditary peripheral neuropathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, autosomal recessive 1; Charcot-Marie-Tooth disease, axonal, type 2S	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	Neurologic	11528396; 14681881; 15290238; 16458836; 16765827; 17431882; 20859832; 21353777; 22157136; 25439726; 25568292

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IGHMBP2 gene.

• Charcot-Marie-Tooth disease axonal type 2S;Autosomal recessive distal spinal muscular atrophy 1 (408 variants)
• Autosomal recessive distal spinal muscular atrophy 1;Charcot-Marie-Tooth disease axonal type 2S (381 variants)
• not provided (336 variants)
• Inborn genetic diseases (226 variants)
• Autosomal recessive distal spinal muscular atrophy 1 (182 variants)
• Charcot-Marie-Tooth disease (144 variants)
• not specified (100 variants)
• Charcot-Marie-Tooth disease axonal type 2S (39 variants)
• Neuronopathy, distal hereditary motor, autosomal dominant (20 variants)
• Distal spinal muscular atrophy (20 variants)
• Peripheral neuropathy (3 variants)
• Spinal muscular atrophy (3 variants)
• IGHMBP2-related disorders (2 variants)
• IGHMBP2-related condition (2 variants)
• Neurodevelopmental disorder (2 variants)
• Progressive muscle weakness;Lower limb muscle weakness;Hammertoe;Difficulty walking;Inability to walk (2 variants)
• Neuronopathy, distal hereditary motor, autosomal dominant 1 (1 variants)
• 7 conditions (1 variants)
• Charcot-Marie-Tooth disease, type I (1 variants)
• IGHMBP2-related neuronopathy (1 variants)
• Autosomal dominant intermediate 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 IGHMBP2 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			9	181	5	195
missense	7	17	429	13	9	475
nonsense	18	6				24
start loss		1				1
frameshift	26	9				35
inframe indel			5			5
splice donor/acceptor (+/-2bp)	6	10	1			17
splice region		2	13	19	1	35
non coding	1		29	94	48	172
Total	58	43	473	288	62

Highest pathogenic variant AF is 0.0000919

Variants in IGHMBP2

This is a list of pathogenic ClinVar variants found in the IGHMBP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-68903885-T-C		Autosomal recessive distal spinal muscular atrophy 1	Benign (Jan 13, 2018)
11-68903904-G-C		not specified	Likely benign (Oct 23, 2017)
11-68903919-C-G		not specified	Likely benign (Oct 27, 2017)
11-68903923-G-C		not specified	Likely benign (Mar 21, 2017)
11-68903925-C-A		Autosomal recessive distal spinal muscular atrophy 1 • not specified	Benign (Jan 13, 2018)
11-68903928-C-T		not specified	Likely benign (Oct 20, 2016)
11-68903939-G-C		not specified	Likely benign (Apr 27, 2017)
11-68903948-C-T			Uncertain significance (Jun 01, 2016)
11-68903949-G-A		Spinal muscular atrophy	Uncertain significance (Jun 14, 2016)
11-68903951-C-T		not specified • Autosomal recessive distal spinal muscular atrophy 1 • Charcot-Marie-Tooth disease • Charcot-Marie-Tooth disease axonal type 2S	Benign (Aug 10, 2021)
11-68903954-T-C		Autosomal recessive distal spinal muscular atrophy 1 • Inborn genetic diseases • Charcot-Marie-Tooth disease axonal type 2S;Autosomal recessive distal spinal muscular atrophy 1	Pathogenic/Likely pathogenic (Aug 04, 2023)
11-68903956-G-A		Charcot-Marie-Tooth disease • Inborn genetic diseases	Uncertain significance (Mar 11, 2021)
11-68903956-G-T		Autosomal recessive distal spinal muscular atrophy 1;Charcot-Marie-Tooth disease axonal type 2S • Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
11-68903958-C-T		Charcot-Marie-Tooth disease axonal type 2S;Autosomal recessive distal spinal muscular atrophy 1	Likely benign (Apr 03, 2018)
11-68903959-T-G		Charcot-Marie-Tooth disease axonal type 2S;Autosomal recessive distal spinal muscular atrophy 1	Uncertain significance (Aug 31, 2022)
11-68903962-G-A		not specified	Uncertain significance (Nov 02, 2016)
11-68903964-A-G		Autosomal recessive distal spinal muscular atrophy 1;Charcot-Marie-Tooth disease axonal type 2S	Likely benign (Sep 18, 2023)
11-68903967-T-A		Charcot-Marie-Tooth disease axonal type 2S;Autosomal recessive distal spinal muscular atrophy 1	Likely benign (Oct 04, 2023)
11-68903986-A-ACC		Spinal muscular atrophy	Likely pathogenic (Jun 17, 2019)
11-68903988-G-A		Autosomal recessive distal spinal muscular atrophy 1;Charcot-Marie-Tooth disease axonal type 2S	Likely benign (Nov 15, 2023)
11-68903988-G-T		Charcot-Marie-Tooth disease	Benign (-)
11-68903991-A-G		Charcot-Marie-Tooth disease axonal type 2S;Autosomal recessive distal spinal muscular atrophy 1	Likely benign (Apr 08, 2023)
11-68903998-C-G		Autosomal recessive distal spinal muscular atrophy 1;Charcot-Marie-Tooth disease axonal type 2S	Uncertain significance (Nov 14, 2023)
11-68903998-C-T		Charcot-Marie-Tooth disease axonal type 2S;Autosomal recessive distal spinal muscular atrophy 1	Likely benign (May 18, 2023)
11-68904002-T-C		Distal spinal muscular atrophy	Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IGHMBP2	protein_coding	protein_coding	ENST00000255078	15	36761

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.02e-16	0.631	125607	0	141	125748	0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.176	580	592	0.980	0.0000399	6378
Missense in Polyphen		192	207.34	0.92604		2161
Synonymous	-1.40	287	258	1.11	0.0000188	2081
Loss of Function	1.81	31	43.9	0.706	0.00000283	464

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000573	0.000570
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000821	0.000816
Finnish	0.000468	0.000416
European (Non-Finnish)	0.000752	0.000721
Middle Eastern	0.000821	0.000816
South Asian	0.000621	0.000425
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 5' to 3' helicase that unwinds RNA and DNA duplices in an ATP-dependent reaction. Acts as a transcription regulator. Required for the transcriptional activation of the flounder liver- type antifreeze protein gene. Exhibits strong binding specificity to the enhancer element B of the flounder antifreeze protein gene intron. Binds to the insulin II gene RIPE3B enhancer region. May be involved in translation (By similarity). DNA-binding protein specific to 5'-phosphorylated single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region. Preferentially binds to the 5'-GGGCT-3' motif. Interacts with tRNA-Tyr. Stimulates the transcription of the human neurotropic virus JCV. {ECO:0000250, ECO:0000269|PubMed:19158098, ECO:0000269|PubMed:19299493}.
• Disease: DISEASE: Charcot-Marie-Tooth disease 2S (CMT2S) [MIM:616155]: An axonal 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). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:25439726}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.199

Intolerance Scores

• loftool: 0.0776
• rvis_EVS: 0.86
• rvis_percentile_EVS: 88.57

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.414
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.818

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ighmbp2
• Phenotype: growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary 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)

Gene ontology

• Biological process: DNA replication;DNA repair;DNA recombination;translation;DNA duplex unwinding;protein homooligomerization
• Cellular component: nucleus;cytoplasm;membrane;axon;growth cone;ribonucleoprotein complex
• Molecular function: tRNA binding;DNA binding;DNA helicase activity;single-stranded DNA binding;RNA binding;protein binding;ATP binding;DNA-dependent ATPase activity;transcription factor binding;RNA-dependent ATPase activity;zinc ion binding;ATP-dependent 5'-3' RNA helicase activity;ribosome binding;ATP-dependent 5'-3' DNA helicase activity