FAM111A

FAM111 trypsin like peptidase A

Basic information

Region (hg38): 11:59142748-59155039

Links

ENSG00000166801 ∙ NCBI:63901 ∙ OMIM:615292 ∙ HGNC:24725 ∙ Uniprot:Q96PZ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant Kenny-Caffey syndrome (Strong), mode of inheritance: AD
• autosomal dominant Kenny-Caffey syndrome (Definitive), mode of inheritance: AD
• autosomal dominant Kenny-Caffey syndrome (Moderate), mode of inheritance: AD
• osteocraniostenosis (Supportive), mode of inheritance: AD
• autosomal dominant Kenny-Caffey syndrome (Supportive), mode of inheritance: AD
• osteocraniostenosis (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Kenny-Caffey syndrome, type 2	AD	Endocrine	Among other findings, individuals may manifest with primary hypoparathyroidism with hypocalcemia (which can be life-threatening), and awareness may allow early management	Craniofacial; Endocrine; Musculoskeletal; Ophthalmologic	23684011

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FAM111A gene.

• not_provided (258 variants)
• Inborn_genetic_diseases (72 variants)
• FAM111A-related_disorder (18 variants)
• not_specified (15 variants)
• Osteocraniostenosis (13 variants)
• Autosomal_dominant_Kenny-Caffey_syndrome (10 variants)
• Congenital_heart_disease (1 variants)
• Hypoparathyroidism (1 variants)
• Skeletal_dysplasia (1 variants)
• Microcephaly (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 FAM111A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001312909.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	56	10	68
missense		7	157	36	17	217
nonsense		1	3	2		6
start loss						0
frameshift			7	10		17
splice donor/acceptor (+/-2bp)			1			1
Total	0	8	170	104	27

Highest pathogenic variant AF is 0.0000136304

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FAM111A	protein_coding	protein_coding	ENST00000528737	2	12292

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00222	0.327	125679	0	2	125681	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0210	324	323	1.00	0.0000161	4101
Missense in Polyphen		75	76.872	0.97565		1050
Synonymous	0.413	106	112	0.950	0.00000560	1093
Loss of Function	-1.21	3	1.43	2.09	6.01e-8	19

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000983	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chromatin-associated protein required for PCNA loading on replication sites. Promotes S-phase entry and DNA synthesis (PubMed:24561620). May directly function at replication forks, explaining why Simian virus 40 (SV40) interacts with FAM111A to overcome host range restriction (PubMed:23093934). {ECO:0000269|PubMed:23093934, ECO:0000269|PubMed:24561620}.
• Disease: DISEASE: Kenny-Caffey syndrome 2 (KCS2) [MIM:127000]: A disorder characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. Clinical features include cortical thickening and medullary stenosis of the tubular bones, delayed closure of fontanels, defective dentition, small eyes with hypermetropia, and frontal bossing with a triangular face. {ECO:0000269|PubMed:23684011, ECO:0000269|PubMed:23996431, ECO:0000269|PubMed:24635597}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Gracile bone dysplasia (GCLEB) [MIM:602361]: A perinatally lethal condition characterized by narrowing of the medullary cavity of the long bones and of the skull, gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia. Most affected individuals who survive beyond the perinatal period develop hypocalcemia with low parathyroid hormone levels. {ECO:0000269|PubMed:23684011}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.239
• rvis_EVS: -0.26
• rvis_percentile_EVS: 34.88

Haploinsufficiency Scores

• pHI: 0.0784
• hipred: N
• hipred_score: 0.112
• ghis: 0.478

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.000122

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fam111a

Gene ontology

• Biological process: DNA replication;viral process;negative regulation of viral genome replication;defense response to virus
• Cellular component: chromatin;fibrillar center;nucleus;cytoplasm
• Molecular function: protein binding