C19orf12

chromosome 19 open reading frame 12

Basic information

Region (hg38): 19:29698937-29715789

Previous symbols: [ "SPG43" ]

Links

ENSG00000131943 ∙ NCBI:83636 ∙ OMIM:614297 ∙ HGNC:25443 ∙ Uniprot:Q9NSK7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration with brain iron accumulation 4 (Strong), mode of inheritance: AD
• neurodegeneration with brain iron accumulation 4 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 43 (Limited), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 4 (Strong), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 4 (Definitive), mode of inheritance: Semidominant
• neurodegeneration with brain iron accumulation 4 (Strong), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 4 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 43 (Limited), mode of inheritance: AR
• hereditary spastic paraplegia 43 (Limited), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 4 (Moderate), mode of inheritance: AD
• neurodegeneration with brain iron accumulation 4 (Definitive), mode of inheritance: AR
• neurodegeneration with brain iron accumulation 4 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration with brain iron accumulation 4; Spastic paraplegia 43	AD/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	21981780; 22508347; 23269600; 23447832; 23494994; 23521069; 23857908; 26187298; 29295770; 30298423; 31087512

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C19orf12 gene.

• Hereditary_spastic_paraplegia_43 (132 variants)
• Neurodegeneration_with_brain_iron_accumulation_4 (60 variants)
• not_provided (55 variants)
• not_specified (19 variants)
• Hereditary_spastic_paraplegia (10 variants)
• Neurodegeneration_with_brain_iron_accumulation (7 variants)
• C19orf12-related_disorder (4 variants)
• Dystonic_disorder (2 variants)
• Tremor (2 variants)
• Inborn_genetic_diseases (2 variants)
• Peripheral_visual_field_loss (2 variants)
• Adult-onset_night_blindness (2 variants)
• Mental_deterioration (2 variants)
• Hereditary_spastic_paraplegia_5A (1 variants)
• Abnormality_of_iron_homeostasis (1 variants)
• Global_developmental_delay (1 variants)
• Intellectual_disability (1 variants)
• Neurofibromatosis,_type_1 (1 variants)
• Abnormal_central_motor_function (1 variants)
• Brain_iron_accummulation (1 variants)
• Neurodegeneration (1 variants)
• Spastic_ataxia (1 variants)
• Neurodegeneration_with_brain_iron_accumulation_2B (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C19orf12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000031448.6. 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				41		41
missense	3	10	70	3	1	87
nonsense	3	2	2			7
start loss			2			2
frameshift	8	9	9			26
splice donor/acceptor (+/-2bp)		3	1			4
Total	14	24	84	44	1

Highest pathogenic variant AF is 0.0000811646

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C19orf12	protein_coding	protein_coding	ENST00000392278	3	14644

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.344	0.604	125714	0	32	125746	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.390	84	94.7	0.887	0.00000631	976
Missense in Polyphen		17	20.886	0.81395		265
Synonymous	-0.785	52	45.3	1.15	0.00000379	322
Loss of Function	1.52	1	4.46	0.224	1.92e-7	55

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000223	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000188	0.000185
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Neurodegeneration with brain iron accumulation 4 (NBIA4) [MIM:614298]: A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA4 results in speech difficulty, extrapyramidal signs, oromandibular and generalized dystonia, and parkinsonism. Most patients have progressive involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor plantar responses. {ECO:0000269|PubMed:21981780, ECO:0000269|PubMed:22508347, ECO:0000269|PubMed:22584950, ECO:0000269|PubMed:22704260, ECO:0000269|PubMed:23269600, ECO:0000269|PubMed:23278385, ECO:0000269|PubMed:23521069, ECO:0000269|PubMed:23857908, ECO:0000269|PubMed:25592411, ECO:0000269|PubMed:26136767, ECO:0000269|PubMed:26187298}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 43, autosomal recessive (SPG43) [MIM:615043]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SP43 is characterized by childhood onset of progressive spasticity affecting the lower and upper limbs. {ECO:0000269|PubMed:23857908}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.0410
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.06

Haploinsufficiency Scores

• pHI: 0.119
• hipred: N
• hipred_score: 0.199
• ghis: 0.392

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: 1600014C10Rik

Gene ontology

• Biological process: autophagy;apoptotic process;response to oxidative stress;mitochondrial calcium ion homeostasis
• Cellular component: mitochondrion;endoplasmic reticulum;cytosol;integral component of membrane;mitochondrial membrane