UniProtKB/SwissProt variant VAR

Barrier-to-autointegration factor
Gene: BANF1
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Variant information Variant position:

12 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Alanine (A) to Threonine (T) at position 12 (A12T, p.Ala12Thr). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from small size and hydrophobic (A) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In NGPS; shows a dramatic reduction in BANF1 protein levels indicating that the mutation impairs protein stability. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs387906871 [ dbSNP | Ensembl ]

Sequence information Variant position:

12 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

89 The length of the canonical sequence.
Location on the sequence:

MTTSQKHRDFV A EPMGEKPVGSLAGIGEVLGK The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         MTTSQKHRDFVAEPMGEKPVGSLAGIGEVLGK

Mouse                         MTTSQKHRDFVAEPMGEKPVGSLAGIGDVLSK

Rat                           MTTSQKHRDFVAEPMGEKPVGSLAGIGDALGK

Bovine                        MTTSQKHRDFVAEPMGEKPVGSLAGIGEVLGK

Zebrafish                     SSTSQKHKDFVAEPMGEKSVMALAGIGEVLGK

Drosophila                    SGTSQKHRNFVAEPMGNKSVTELAGIGETLGG

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 89	Barrier-to-autointegration factor
Initiator methionine	1 – 1	Removed; alternate
Chain	2 – 89	Barrier-to-autointegration factor, N-terminally processed
Modified residue	1 – 1	N-acetylmethionine
Modified residue	2 – 2	(Microbial infection) Phosphothreonine; by viral VacV B1 kinase
Modified residue	2 – 2	N-acetylthreonine; in Barrier-to-autointegration factor, N-terminally processed
Modified residue	2 – 2	Phosphothreonine; by VRK1 and VRK2
Modified residue	3 – 3	(Microbial infection) Phosphothreonine; by viral VacV B1 kinase
Modified residue	3 – 3	Phosphothreonine; by VRK1 and VRK2
Modified residue	4 – 4	Phosphoserine; by viral VacV B1 kinase, VRK1 and VRK2
Mutagenesis	4 – 4	S -> A. Delayed phosphorylation with a 10-fold decrease in the initial phosphorylation rate. 71% loss of binding to lamin A.
Mutagenesis	4 – 4	S -> D. 75% cytoplasmic localization.
Mutagenesis	4 – 4	S -> E. Complete loss of phosphorylation and mislocalization of EMD in nucleus.
Mutagenesis	6 – 6	K -> A. Complete loss of LEMD3/MAN1 and histone H1/H3 binding.
Mutagenesis	6 – 6	K -> E. Complete loss of dsDNA and LEMD3/MAN1 binding.
Mutagenesis	8 – 8	R -> A. Enhances histone H1/H3 binding.
Mutagenesis	8 – 8	R -> E. Complete loss of LEMD3/MAN1 binding.
Mutagenesis	9 – 9	D -> A. Reduces binding to dsDNA, LEMD3/MAN1 and histone H1/H3. Reduced interaction with PARP1.
Mutagenesis	14 – 14	P -> A. No effect on LEMD3/MAN1 and enhances histone H1/H3 binding.
Mutagenesis	18 – 18	K -> A. No effect on histone H1/H3 binding.
Mutagenesis	25 – 25	G -> E. Complete loss of dsDNA, EMD, histone H1/H3 and LEMD3/MAN1 binding.
Mutagenesis	25 – 25	G -> Q. Complete loss of EMD binding and reduces dsDNA binding.
Mutagenesis	26 – 26	I -> A. Reduces histone H1/H3 and LEMD3/MAN1 binding. Fails to promote HIV-1 genome integration.
Mutagenesis	26 – 26	I -> K. Fails to promote HIV-1 genome integration.
Mutagenesis	27 – 27	G -> E. Fails to bind dsDNA.
Mutagenesis	27 – 27	G -> Q. Reduces binding to dsDNA.
Mutagenesis	29 – 29	V -> A. No effect on histone H1/H3 binding.
Mutagenesis	32 – 32	K -> E. No effect on histone H1/H3 binding.

Literature citations
Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome.
Puente X.S.; Quesada V.; Osorio F.G.; Cabanillas R.; Cadinanos J.; Fraile J.M.; Ordonez G.R.; Puente D.A.; Gutierrez-Fernandez A.; Fanjul-Fernandez M.; Levy N.; Freije J.M.; Lopez-Otin C.;
Am. J. Hum. Genet. 88:650-656(2011)
Cited for: VARIANT NGPS THR-12;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75531: Variant p.Ala12Thr