CSTB

cystatin B, the group of Cystatins, type 1

Basic information

Region (hg38): 21:43772511-43776330

Previous symbols: [ "EPM1", "STFB" ]

Links

ENSG00000160213 ∙ NCBI:1476 ∙ OMIM:601145 ∙ HGNC:2482 ∙ Uniprot:P04080 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Unverricht-Lundborg syndrome (Definitive), mode of inheritance: AR
• Unverricht-Lundborg syndrome (Strong), mode of inheritance: AR
• keratolytic winter erythema (Moderate), mode of inheritance: AD
• Unverricht-Lundborg syndrome (Supportive), mode of inheritance: AR
• autosomal recessive hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AR
• Unverricht-Lundborg syndrome (Definitive), mode of inheritance: AR
• genetic developmental and epileptic encephalopathy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoclonic epilepsy of Unverricht and Lundborg	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	6137660; 8596935; 9012407; 9054946; 9126745; 9090386; 9527146; 9529356; 9814834; 9932979; 12427904; 12707458; 15508934; 15778103; 18325013; 20301321; 20593193
Some medications (reports include valproate, N-acetylcysteine, levetiracetam) can result in marked improvement, but phenytoin can worsen neurologic manifestations, and can even increase cerebellar degeneration; Other medications (eg, carbamazepine, oxcarbazepine, tiagabine, vigabatrin, gabapentin, pregabalin) can worsen myoclonus/myoclonic seizures

ClinVar

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

• Progressive_myoclonic_epilepsy (108 variants)
• not_provided (40 variants)
• Unverricht-Lundborg_syndrome (25 variants)
• Inborn_genetic_diseases (22 variants)
• not_specified (8 variants)
• CSTB-related_disorder (4 variants)
• Dyskinesia (2 variants)
• Dystonic_disorder (1 variants)
• Motor_delay (1 variants)
• Self-limited_epilepsy_with_centrotemporal_spikes (1 variants)
• Chorea (1 variants)
• Progressive_microcephaly (1 variants)
• Aplasia/Hypoplasia_of_the_corpus_callosum (1 variants)
• Microcephaly (1 variants)
• Severe_global_developmental_delay (1 variants)
• Intellectual_disability,_severe (1 variants)
• Cerebral_dysmyelination (1 variants)
• Encephalopathy (1 variants)
• Global_brain_atrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSTB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000100.4. 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		2	1	31		34
missense	2	1	53	2		58
nonsense	1	5				6
start loss		1				1
frameshift	3	4	1			8
splice donor/acceptor (+/-2bp)	1	1	2			4
Total	7	14	57	33	0

Highest pathogenic variant AF is 0.0002983053

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSTB	protein_coding	protein_coding	ENST00000291568	3	3934

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00656	0.531	125699	0	42	125741	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0172	52	52.4	0.993	0.00000299	645
Missense in Polyphen		11	14.592	0.75384		206
Synonymous	0.577	21	24.6	0.852	0.00000182	175
Loss of Function	0.0148	3	3.03	0.991	1.30e-7	37

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000325	0.000325
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This is an intracellular thiol proteinase inhibitor. Tightly binding reversible inhibitor of cathepsins L, H and B.
• Disease: DISEASE: Epilepsy, progressive myoclonic 1 (EPM1) [MIM:254800]: An autosomal recessive disorder characterized by severe, stimulus- sensitive myoclonus and tonic-clonic seizures. The onset, occurring between 6 and 13 years of age, is characterized by convulsions. Myoclonus begins 1 to 5 years later. The twitchings occur predominantly in the proximal muscles of the extremities and are bilaterally symmetrical, although asynchronous. At first small, they become late in the clinical course so violent that the victim is thrown to the floor. Mental deterioration and eventually dementia develop. {ECO:0000269|PubMed:9012407}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neutrophil degranulation;Innate Immune System;Immune System;EGFR1 (Consensus)

Recessive Scores

• pRec: 0.502

Intolerance Scores

• loftool: 0.662
• rvis_EVS: 0.26
• rvis_percentile_EVS: 69.83

Haploinsufficiency Scores

• pHI: 0.146
• hipred: N
• hipred_score: 0.307
• ghis: 0.397

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.691

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cstb
• Phenotype: vision/eye 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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype; cellular phenotype

Gene ontology

• Biological process: adult locomotory behavior;negative regulation of peptidase activity;negative regulation of endopeptidase activity;neutrophil degranulation;negative regulation of proteolysis
• Cellular component: extracellular region;extracellular space;nucleolus;cytoplasm;cytosol;secretory granule lumen;collagen-containing extracellular matrix;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: protease binding;RNA binding;endopeptidase inhibitor activity;cysteine-type endopeptidase inhibitor activity