NBAS

NBAS subunit of NRZ tethering complex, the group of NRZ tethering complex

Basic information

Region (hg38): 2:15166916-15561340

Links

ENSG00000151779 ∙ NCBI:51594 ∙ OMIM:608025 ∙ HGNC:15625 ∙ Uniprot:A2RRP1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• infantile liver failure syndrome 2 (Definitive), mode of inheritance: AR
• short stature-optic atrophy-Pelger-Huët anomaly syndrome (Supportive), mode of inheritance: AR
• infantile liver failure syndrome 2 (Supportive), mode of inheritance: AR
• short stature-optic atrophy-Pelger-Huët anomaly syndrome (Definitive), mode of inheritance: AR
• short stature-optic atrophy-Pelger-Huët anomaly syndrome (Strong), mode of inheritance: AR
• infantile liver failure syndrome 2 (Strong), mode of inheritance: AR
• short stature-optic atrophy-Pelger-Huët anomaly syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Infantile liver failure syndrome 2; Short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome)	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; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic	20577004; 26073778

ClinVar

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

• not_provided (2346 variants)
• Inborn_genetic_diseases (366 variants)
• Infantile_liver_failure_syndrome_2 (108 variants)
• NBAS-related_disorder (90 variants)
• Short_stature-optic_atrophy-Pelger-Hu�t_anomaly_syndrome (85 variants)
• not_specified (52 variants)
• Acute_infantile_liver_failure_due_to_synthesis_defect_of_mtDNA-encoded_proteins (24 variants)
• Retinal_dystrophy (12 variants)
• Optic_atrophy (6 variants)
• Infantile_liver_failure (3 variants)
• Leber_congenital_amaurosis (2 variants)
• Neurodevelopmental_disorder (2 variants)
• See_cases (2 variants)
• Monogenic_short_statue (2 variants)
• Schizophrenia (1 variants)
• Pituitary_stalk_interruption_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NBAS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015909.4. 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	1	1	10	576	23	611
missense	2	21	912	253	11	1199
nonsense	55	23	1			79
start loss		2				2
frameshift	52	28	1			81
splice donor/acceptor (+/-2bp)	1	55				56
Total	111	130	924	829	34

Highest pathogenic variant AF is 0.00025660224

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NBAS	protein_coding	protein_coding	ENST00000281513	52	394423

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.02e-43	0.996	125350	0	398	125748	0.00158

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.875	1342	1.25e+3	1.07	0.0000677	15446
Missense in Polyphen		332	341.23	0.97295		4105
Synonymous	-3.17	552	465	1.19	0.0000252	4532
Loss of Function	3.79	90	138	0.652	0.00000742	1634

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00360	0.00359
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000925	0.000925
Finnish	0.00148	0.00148
European (Non-Finnish)	0.00185	0.00185
Middle Eastern	0.000925	0.000925
South Asian	0.000751	0.000752
Other	0.00310	0.00310

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER (PubMed:19369418). {ECO:0000269|PubMed:19369418, ECO:0000305}.
• Disease: DISEASE: Infantile liver failure syndrome 2 (ILFS2) [MIM:616483]: A form of infantile liver failure syndrome, a life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis. {ECO:0000269|PubMed:26073778}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=NBAS mutations have been found in a multisystem disease affecting the liver, eye, immune system, connective tissue, and bone. Clinical manifestations include a progeroid appearance, short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, cervical instability, myelopathy, elevated transaminases, hypogammaglobulinemia, reduced natural killer cells, Pelger-Huet anomaly of granulocytes, and in some cases retinal dystrophy and optic atrophy. {ECO:0000269|PubMed:26286438}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Intolerance Scores

• loftool: 0.944
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.33

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.426
• ghis: 0.519

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0491

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nbas

Zebrafish Information Network

• Gene name: nbas
• Affected structure: somite
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;protein transport;negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;membrane;Dsl1/NZR complex
• Molecular function: SNARE binding